17-40819076-G-A

Position:

chr17-40819076-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000421.5(KRT10):c.1459C>T(p.His487Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,329,148 control chromosomes in the GnomAD database, including 328,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 36189 hom., cov: 24)

Exomes 𝑓: 0.73 ( 292489 hom. )

Consequence

KRT10
NM_000421.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.352

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7027287E-7).

BP6

Variant 17-40819076-G-A is Benign according to our data. Variant chr17-40819076-G-A is described in ClinVar as [Benign]. Clinvar id is 1300082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1459C>T	p.His487Tyr	missense_variant	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1459C>T	p.His487Tyr	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.1459C>T	p.His487Tyr	missense_variant	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10-AS1	ENST00000301665.9 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

102431

AN:

138012

Hom.:

36162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.839

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.737

Gnomad FIN

AF:

0.744

Gnomad MID

AF:

0.784

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.737

GnomAD3 exomes

AF:

0.663

AC:

48544

AN:

73236

Hom.:

16254

AF XY:

0.676

AC XY:

28965

AN XY:

42872

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.644

Gnomad EAS exome

AF:

0.499

Gnomad SAS exome

AF:

0.721

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.691

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.725

AC:

864081

AN:

1191034

Hom.:

292489

Cov.:

109

AF XY:

0.726

AC XY:

426141

AN XY:

587340

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.474

Gnomad4 SAS exome

AF:

0.739

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.732

Gnomad4 OTH exome

AF:

0.721

GnomAD4 genome

AF:

0.742

AC:

102506

AN:

138114

Hom.:

36189

Cov.:

AF XY:

0.739

AC XY:

49637

AN XY:

67194

show subpopulations

Gnomad4 AFR

AF:

0.838

Gnomad4 AMR

AF:

0.636

Gnomad4 ASJ

AF:

0.682

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.744

Gnomad4 NFE

AF:

0.723

Gnomad4 OTH

AF:

0.736

Alfa

AF:

0.550

Hom.:

1389

Bravo

AF:

0.717

ExAC

AF:

0.213

AC:

7565

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epidermolytic ichthyosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Annular epidermolytic ichthyosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Congenital reticular ichthyosiform erythroderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.5

DANN

Benign

0.94

DEOGEN2

Benign

0.094

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.21

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.62

REVEL

Benign

0.20

Sift

Benign

0.27

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.064

MPC

0.49

ClinPred

0.011

GERP RS

-1.5

Varity_R

0.21

gMVP

0.40

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