Variant rs3826550 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000526.5(KRT14):c.280G>A(p.Ala94Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,682 control chromosomes in the GnomAD database, including 141,439 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.40 ( 12731 hom., cov: 32)

Exomes 𝑓: 0.41 ( 128708 hom. )

Consequence

KRT14
NM_000526.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.297

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017464757).

BP6

Variant 17-41586555-C-T is Benign according to our data. Variant chr17-41586555-C-T is described in ClinVar as [Benign]. Clinvar id is 66336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586555-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.280G>A	p.Ala94Thr	missense_variant	1/8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 link	c.280G>A	p.Ala94Thr	missense_variant	1/8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60658

AN:

151884

Hom.:

12729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.0508

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.348

AC:

86994

AN:

250158

Hom.:

17052

AF XY:

0.353

AC XY:

47729

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.0543

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.411

AC:

600059

AN:

1461680

Hom.:

128708

Cov.:

103

AF XY:

0.408

AC XY:

296494

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.0406

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.408

GnomAD4 genome

AF:

0.399

AC:

60691

AN:

152002

Hom.:

12731

Cov.:

AF XY:

0.391

AC XY:

29044

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.436

Gnomad4 EAS

AF:

0.0507

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.440

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.430

Hom.:

6084

Bravo

AF:

0.397

TwinsUK

AF:

0.442

AC:

1639

ALSPAC

AF:

0.445

AC:

1716

ExAC

AF:

0.350

AC:

42413

Asia WGS

AF:

0.168

AC:

586

AN:

3478

EpiCase

AF:

0.453

EpiControl

AF:

0.442

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 9989794, 25040198, 20128788) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.067

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.84

REVEL

Uncertain

0.32

Sift

Benign

0.41

Sift4G

Benign

0.18

Polyphen

0.048

Vest4

0.10

MPC

0.46

ClinPred

0.013

GERP RS

5.1

Varity_R

0.083

gMVP

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over