Genetic Variant NM_000421.5:c.1460A>C (chr17-40819075-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000421.5(KRT10):c.1460A>C(p.His487Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,215,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

KRT10
NM_000421.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031967282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1460A>C	p.His487Pro	missense_variant	Exon 7 of 8	ENST00000269576.6	NP_000412.4	P13645

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 link	c.1460A>C	p.His487Pro	missense_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.0000562

AC:

AN:

106736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000899

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0123

Gnomad NFE

AF:

0.0000423

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000664

AC:

AN:

61774

Hom.:

AF XY:

0.000577

AC XY:

AN XY:

36374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000387

Gnomad EAS exome

AF:

0.000546

Gnomad SAS exome

AF:

0.000695

Gnomad FIN exome

AF:

0.000474

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.0000622

AC:

AN:

1108448

Hom.:

Cov.:

AF XY:

0.0000604

AC XY:

AN XY:

546732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000821

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.000158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000484

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000588

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000562

AC:

AN:

106812

Hom.:

Cov.:

AF XY:

0.0000768

AC XY:

AN XY:

52108

show subpopulations

Gnomad4 AFR

AF:

0.0000311

Gnomad4 AMR

AF:

0.0000898

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000423

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000675

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Benign

5.9

DANN

Benign

0.54

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.17

M_CAP

Benign

0.061

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.30

REVEL

Benign

0.19

Sift

Uncertain

0.010

Sift4G

Benign

0.20

Polyphen

0.0050

Vest4

0.21

MVP

0.58

MPC

0.66

ClinPred

0.027

GERP RS

1.1

Varity_R

0.43

gMVP

0.53

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