Variant rs142137272 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000526.5(KRT14):c.202G>A(p.Gly68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,608,828 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 14 hom. )

Consequence

KRT14
NM_000526.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.381

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008318633).

BP6

Variant 17-41586633-C-T is Benign according to our data. Variant chr17-41586633-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 256363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 linkuse as main transcript	c.202G>A	p.Gly68Ser	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 linkuse as main transcript	c.202G>A	p.Gly68Ser	missense_variant	1/8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

331

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00248

AC:

556

AN:

223748

Hom.:

AF XY:

0.00244

AC XY:

297

AN XY:

121862

show subpopulations

Gnomad AFR exome

AF:

0.000506

Gnomad AMR exome

AF:

0.00366

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000103

Gnomad FIN exome

AF:

0.000644

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00301

AC:

4377

AN:

1456542

Hom.:

Cov.:

100

AF XY:

0.00290

AC XY:

2101

AN XY:

724406

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.00358

Gnomad4 ASJ exome

AF:

0.0102

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.000530

Gnomad4 NFE exome

AF:

0.00337

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152286

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00313

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.00253

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00281

AC:

ExAC

AF:

0.00209

AC:

251

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

REVEL

Benign

0.28

Sift

Benign

0.50

Sift4G

Benign

0.13

Polyphen

0.0030

Vest4

0.23

MVP

0.75

MPC

0.47

ClinPred

0.018

GERP RS

3.9

Varity_R

0.049

gMVP

0.83

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