Variant 17-41518338-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002275.4(KRT15):c.490C>T(p.Arg164Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,611,124 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 2 hom. )

Consequence

KRT15
NM_002275.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

KRT15 (HGNC:6421): (keratin 15) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region on chromosome 17q21.2. [provided by RefSeq, Jul 2008]

KRT15 links:

KRT15 (HGNC:):

KRT15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT15	NM_002275.4 linkuse as main transcript	c.490C>T	p.Arg164Trp	missense_variant	1/8	ENST00000254043.8	NP_002266.3	P19012-1B3KVF5
KRT15	XM_011524784.4 linkuse as main transcript	c.490C>T	p.Arg164Trp	missense_variant	1/8		XP_011523086.1
KRT15	XM_017024614.3 linkuse as main transcript	c.490C>T	p.Arg164Trp	missense_variant	1/8		XP_016880103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT15	ENST00000254043.8 linkuse as main transcript	c.490C>T	p.Arg164Trp	missense_variant	1/8	1	NM_002275.4	ENSP00000254043.3		P19012-1

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000367

AC:

AN:

250358

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000601

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000692

AC:

1009

AN:

1458908

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

451

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000778

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.000545

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000465

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.490C>T (p.R164W) alteration is located in exon 1 (coding exon 1) of the KRT15 gene. This alteration results from a C to T substitution at nucleotide position 490, causing the arginine (R) at amino acid position 164 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.75

D;D

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

4.2

H;H

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.46

MVP

0.92

MPC

0.18

ClinPred

0.91

GERP RS

3.2

Varity_R

0.67

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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