Variant 17-40818859-C-CCGCCGTATCCGCCGCCGGAGCTGCTGCCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM4BP6_Moderate

The NM_000421.5(KRT10):c.1675_1676insCAGGCAGCAGCTCCGGCGGCGGATACGGCG(p.Gly558_Gly559insAlaGlySerSerSerGlyGlyGlyTyrGly) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 151,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

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 Uncertain_significance. Variant got 0 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

BP6

Variant 17-40818859-C-CCGCCGTATCCGCCGCCGGAGCTGCTGCCTG is Benign according to our data. Variant chr17-40818859-C-CCGCCGTATCCGCCGCCGGAGCTGCTGCCTG is described in ClinVar as [Likely_benign]. Clinvar id is 2151211.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1675_1676insCAGGCAGCAGCTCCGGCGGCGGATACGGCG	p.Gly558_Gly559insAlaGlySerSerSerGlyGlyGlyTyrGly	inframe_insertion	7/8	ENST00000269576.6
KRT10	NM_001379366.1 linkuse as main transcript	c.1675_1676insCAGGCAGCAGCTCCGGCGGCGGATACGGCG	p.Gly558_Gly559insAlaGlySerSerSerGlyGlyGlyTyrGly	inframe_insertion	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT10	ENST00000269576.6 linkuse as main transcript	c.1675_1676insCAGGCAGCAGCTCCGGCGGCGGATACGGCG	p.Gly558_Gly559insAlaGlySerSerSerGlyGlyGlyTyrGly	inframe_insertion	7/8	1	NM_000421.5	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1675_1676insCAGGCAGCAGCTCCGGCGGCGGATACGGCG	p.Gly558_Gly559insAlaGlySerSerSerGlyGlyGlyTyrGly	inframe_insertion	7/8	2		A2

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000460

AC:

AN:

195444

Hom.:

AF XY:

0.000616

AC XY:

AN XY:

110402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000426

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000243

AC:

340

AN:

1400786

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

257

AN XY:

697330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00375

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000266

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000152

AC:

AN:

151664

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Invitae

Aug 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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