NM_000526.5:c.369T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000526.5(KRT14):c.369T>C(p.Asn123Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,613,754 control chromosomes in the GnomAD database, including 283,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25950 hom., cov: 31)

Exomes 𝑓: 0.59 ( 257118 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.276

Publications

17 publications found

Variant links:

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp
Naegeli-Franceschetti-Jadassohn syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp
dermatopathia pigmentosa reticularis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-41586466-A-G is Benign according to our data. Variant chr17-41586466-A-G is described in ClinVar as Benign. ClinVar VariationId is 66346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.369T>C	p.Asn123Asn	synonymous_variant	Exon 1 of 8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 link	c.369T>C	p.Asn123Asn	synonymous_variant	Exon 1 of 8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87247

AN:

151762

Hom.:

25934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.948

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.560

GnomAD2 exomes

AF:

0.644

AC:

161967

AN:

251458

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.945

Gnomad FIN exome

AF:

0.666

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.596

GnomAD4 exome

AF:

0.586

AC:

857284

AN:

1461874

Hom.:

257118

Cov.:

AF XY:

0.590

AC XY:

428742

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.472

AC:

15803

AN:

33480

American (AMR)

AF:

0.764

AC:

34163

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

14714

AN:

26136

East Asian (EAS)

AF:

0.959

AC:

38083

AN:

39700

South Asian (SAS)

AF:

0.716

AC:

61718

AN:

86256

European-Finnish (FIN)

AF:

0.665

AC:

35533

AN:

53420

Middle Eastern (MID)

AF:

0.506

AC:

2915

AN:

5766

European-Non Finnish (NFE)

AF:

0.557

AC:

619023

AN:

1112002

Other (OTH)

AF:

0.585

AC:

35332

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

26012

52023

78035

104046

130058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17474

34948

52422

69896

87370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.575

AC:

87307

AN:

151880

Hom.:

25950

Cov.:

AF XY:

0.584

AC XY:

43331

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.473

AC:

19564

AN:

41394

American (AMR)

AF:

0.677

AC:

10340

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1947

AN:

3466

East Asian (EAS)

AF:

0.948

AC:

4873

AN:

5140

South Asian (SAS)

AF:

0.735

AC:

3539

AN:

4812

European-Finnish (FIN)

AF:

0.658

AC:

6969

AN:

10584

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38045

AN:

67896

Other (OTH)

AF:

0.564

AC:

1189

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1797

3595

5392

7190

8987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.557

Hom.:

10161

Bravo

AF:

0.573

EpiCase

AF:

0.547

EpiControl

AF:

0.556

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epithelial Biology; Institute of Medical Biology, Singapore

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epidermolysis bullosa simplex 1A, generalized severe;C0080333:Epidermolysis bullosa simplex 1C, localized;C0343111:Naegeli-Franceschetti-Jadassohn syndrome;C0406778:Dermatopathia pigmentosa reticularis;C3715082:Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive;C5561924:Epidermolysis bullosa simplex, Koebner type

Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.8

(source)

DANN

Benign

0.57

PhyloP100

-0.28

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over