Variant 17-40818811-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000421.5(KRT10):c.1724G>T(p.Gly575Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,598,260 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

KRT10
NM_000421.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

KRT10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054396093).

BP6

Variant 17-40818811-C-A is Benign according to our data. Variant chr17-40818811-C-A is described in ClinVar as [Benign]. Clinvar id is 1598575.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1724G>T	p.Gly575Val	missense_variant	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1724G>T	p.Gly575Val	missense_variant	7/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 linkuse as main transcript	c.1724G>T	p.Gly575Val	missense_variant	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1724G>T	p.Gly575Val	missense_variant	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00107

AC:

247

AN:

230034

Hom.:

AF XY:

0.000999

AC XY:

127

AN XY:

127114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000600

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.00204

GnomAD4 exome

AF:

0.00139

AC:

2006

AN:

1446094

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

949

AN XY:

719798

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000863

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152166

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000833

AC:

ExAC

AF:

0.000699

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KRT10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.088

T;T

Eigen

Benign

0.055

Eigen_PC

Benign

-0.0013

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0054

T;T

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.23

.;N

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.014

.;D

Polyphen

1.0

.;D

Vest4

0.34

MVP

0.90

MPC

0.53

ClinPred

0.074

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.76

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