Variant 17-41620565-GAA-GAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_000422.3(KRT17):c.1182-9_1182-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 145,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT17
NM_000422.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.262

Variant links:

Genes affected

KRT17 (HGNC:6427): (keratin 17) This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. [provided by RefSeq, Aug 2008]

KRT17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 17-41620565-G-GAA is Benign according to our data. Variant chr17-41620565-G-GAA is described in ClinVar as [Likely_benign]. Clinvar id is 3037508.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT17	NM_000422.3 link	c.1182-9_1182-8dupTT		splice_region_variant, intron_variant	Intron 6 of 7	ENST00000311208.13	NP_000413.1	Q04695Q14666

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT17	ENST00000311208.13 link	c.1182-8_1182-7insTT	splice_region_variant, intron_variant	Intron 6 of 7	1	NM_000422.3	ENSP00000308452.8	Q04695
KRT17	ENST00000648859.1 link	c.171-8_171-7insTT	splice_region_variant, intron_variant	Intron 1 of 1			ENSP00000497161.1	A0A3B3IS58
KRT17	ENST00000493253.5 link	n.1569-8_1569-7insTT	splice_region_variant, intron_variant	Intron 5 of 6	2
KRT17	ENST00000649249.1 link	n.458-8_458-7insTT	splice_region_variant, intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000688

AC:

AN:

145366

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

118

AN:

1164332

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

581222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000360

Gnomad4 AMR exome

AF:

0.0000557

Gnomad4 ASJ exome

AF:

0.000235

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.00000688

AC:

AN:

145366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70450

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KRT17-related disorder

Benign:1

May 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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