Genetic Variant KRT10:p.Ser547Cys (chr17-40818895-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000421.5(KRT10):c.1640C>G(p.Ser547Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. SG547SAAAAAPAADTAAAAAPAADR?) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

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:

KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRT10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1888682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1640C>G	p.Ser547Cys	missense_variant	Exon 7 of 8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 link	c.1640C>G	p.Ser547Cys	missense_variant	Exon 7 of 8		NP_001366295.1
KRT10-AS1	NR_160887.1 link	n.-250G>C		upstream_gene_variant
KRT10-AS1	NR_160888.1 link	n.-250G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 link	c.1640C>G	p.Ser547Cys	missense_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

87472

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1182648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

581874

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000229

AC:

AN:

87472

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

42602

show subpopulations

Gnomad4 AFR

AF:

0.000126

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.5

DANN

Benign

0.47

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.2

.;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.060

.;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.14

.;T

Polyphen

0.95

.;P

Vest4

0.18

MutPred

0.40

.;Loss of phosphorylation at S547 (P = 6e-04);

MVP

0.66

MPC

0.41

ClinPred

0.46

GERP RS

-0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over