Variant 17-40818906-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000421.5(KRT10):c.1629G>C(p.Gly543=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,110,904 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0099 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-40818906-C-G is Benign according to our data. Variant chr17-40818906-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1569698.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.328 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00994 (11044/1110904) while in subpopulation AFR AF= 0.0256 (490/19130). AF 95% confidence interval is 0.0237. There are 12 homozygotes in gnomad4_exome. There are 5328 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1629G>C	p.Gly543=	synonymous_variant	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1629G>C	p.Gly543=	synonymous_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.1629G>C	p.Gly543=	synonymous_variant	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1629G>C	p.Gly543=	synonymous_variant	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

710

AN:

84274

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00324

Gnomad ASJ

AF:

0.00321

Gnomad EAS

AF:

0.0347

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00877

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.0108

GnomAD3 exomes

AF:

0.00122

AC:

104

AN:

85572

Hom.:

AF XY:

0.00131

AC XY:

AN XY:

48744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00340

Gnomad SAS exome

AF:

0.000842

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00994

AC:

11044

AN:

1110904

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

5328

AN XY:

544712

show subpopulations

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.00564

Gnomad4 ASJ exome

AF:

0.00825

Gnomad4 EAS exome

AF:

0.0121

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.00333

Gnomad4 NFE exome

AF:

0.00960

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00841

AC:

709

AN:

84352

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

327

AN XY:

41042

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.00323

Gnomad4 ASJ

AF:

0.00321

Gnomad4 EAS

AF:

0.0348

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.3

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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