Variant chr17-40818411-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001379366.1(KRT10):c.1840A>G(p.Met614Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,610,872 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 56 hom. )

Consequence

KRT10
NM_001379366.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.292

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029123127).

BP6

Variant 17-40818411-T-C is Benign according to our data. Variant chr17-40818411-T-C is described in ClinVar as [Benign]. Clinvar id is 1286761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 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.*65A>G		3_prime_UTR_variant	8/8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 linkuse as main transcript	c.1840A>G	p.Met614Val	missense_variant	8/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576 linkuse as main transcript	c.*65A>G		3_prime_UTR_variant	8/8	1	NM_000421.5	ENSP00000269576.5		P13645
KRT10	ENST00000635956.2 linkuse as main transcript	c.1840A>G	p.Met614Val	missense_variant	8/8	2		ENSP00000490524.2		A0A1B0GVI3

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2284

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0520

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.00161

AC:

2341

AN:

1458550

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1026

AN XY:

725448

show subpopulations

Gnomad4 AFR exome

AF:

0.0540

Gnomad4 AMR exome

AF:

0.00343

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.0150

AC:

2291

AN:

152322

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1077

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0520

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00803

Hom.:

Bravo

AF:

0.0171

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0506

AC:

ESP6500EA

AF:

0.00

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0029

GERP RS

4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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