Variant 17-40818434-G-A 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.1817C>T(p.Pro606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,613,194 control chromosomes in the GnomAD database, including 395 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 0.028 ( 231 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 164 hom. )

Consequence

KRT10
NM_001379366.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.48

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=0.0023261607).

BP6

Variant 17-40818434-G-A is Benign according to our data. Variant chr17-40818434-G-A is described in ClinVar as [Benign]. Clinvar id is 1283470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0944 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.*42C>T		3_prime_UTR_variant	8/8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 linkuse as main transcript	c.1817C>T	p.Pro606Leu	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.*42C>T		3_prime_UTR_variant	8/8	1	NM_000421.5	ENSP00000269576.5		P13645
KRT10	ENST00000635956.2 linkuse as main transcript	c.1817C>T	p.Pro606Leu	missense_variant	8/8	2		ENSP00000490524.2		A0A1B0GVI3

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4209

AN:

151990

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00692

AC:

1720

AN:

248664

Hom.:

AF XY:

0.00476

AC XY:

641

AN XY:

134586

show subpopulations

Gnomad AFR exome

AF:

0.0958

Gnomad AMR exome

AF:

0.00362

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00277

AC:

4041

AN:

1461086

Hom.:

164

Cov.:

AF XY:

0.00232

AC XY:

1685

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.0987

Gnomad4 AMR exome

AF:

0.00447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.00648

GnomAD4 genome

AF:

0.0277

AC:

4211

AN:

152108

Hom.:

231

Cov.:

AF XY:

0.0268

AC XY:

1991

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0969

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0883

AC:

389

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00849

AC:

1031

Asia WGS

AF:

0.00635

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 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.083

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0023

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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