Variant 17-41620795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000422.3(KRT17):c.1045G>A(p.Val349Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,613,122 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 6 hom. )

Consequence

KRT17
NM_000422.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.160

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009829462).

BP6

Variant 17-41620795-C-T is Benign according to our data. Variant chr17-41620795-C-T is described in ClinVar as [Benign]. Clinvar id is 1581086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000624 (95/152344) while in subpopulation EAS AF= 0.016 (83/5188). AF 95% confidence interval is 0.0132. There are 1 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1045G>A	p.Val349Met	missense_variant	6/8	ENST00000311208.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.1045G>A	p.Val349Met	missense_variant	6/8	1	NM_000422.3	P1
KRT17	ENST00000648859.1 linkuse as main transcript	c.37G>A	p.Val13Met	missense_variant	1/2
KRT17	ENST00000493253.5 linkuse as main transcript	n.1432G>A		non_coding_transcript_exon_variant	5/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.321G>A		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00120

AC:

302

AN:

250894

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0158

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000333

AC:

487

AN:

1460778

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

239

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0108

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000624

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000630

Hom.:

Bravo

AF:

0.000842

ExAC

AF:

0.00129

AC:

157

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.17

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

1.0

N;D

PrimateAI

Benign

0.46

Polyphen

0.32

B;B;.

Vest4

0.37, 0.44

MVP

0.87

MPC

0.44

ClinPred

0.044

GERP RS

4.0

Varity_R

0.11

gMVP

0.71

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