Variant 17-40818897-G-T 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_000421.5(KRT10):c.1638C>A(p.Ser546Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,145,706 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S546G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00064 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.645

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003172636).

BP6

Variant 17-40818897-G-T is Benign according to our data. Variant chr17-40818897-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1191794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1638C>A	p.Ser546Arg	missense_variant	7/8	ENST00000269576.6
KRT10	NM_001379366.1 linkuse as main transcript	c.1638C>A	p.Ser546Arg	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT10	ENST00000269576.6 linkuse as main transcript	c.1638C>A	p.Ser546Arg	missense_variant	7/8	1	NM_000421.5	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1638C>A	p.Ser546Arg	missense_variant	7/8	2		A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

93600

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000879

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000837

Gnomad SAS

AF:

0.00152

Gnomad FIN

AF:

0.000273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000164

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00876

AC:

986

AN:

112550

Hom.:

AF XY:

0.00897

AC XY:

567

AN XY:

63198

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.0271

Gnomad SAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.00897

Gnomad NFE exome

AF:

0.00823

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.000642

AC:

735

AN:

1145706

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

439

AN XY:

564090

show subpopulations

Gnomad4 AFR exome

AF:

0.00253

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00144

Gnomad4 EAS exome

AF:

0.00283

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.000321

Gnomad4 OTH exome

AF:

0.000823

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000363

AC:

AN:

93680

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

AN XY:

45790

show subpopulations

Gnomad4 AFR

AF:

0.000876

Gnomad4 AMR

AF:

0.000274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000840

Gnomad4 SAS

AF:

0.00152

Gnomad4 FIN

AF:

0.000273

Gnomad4 NFE

AF:

0.000164

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0134

AC:

1353

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 19, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.22

CADD

Benign

4.8

DANN

Benign

0.58

DEOGEN2

Benign

0.079

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.24

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.60

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

Polyphen

0.61

.;P

Vest4

0.13

MutPred

0.40

.;Loss of phosphorylation at S546 (P = 4e-04);

MPC

0.47

ClinPred

0.0096

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.11

gMVP

0.43

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