Variant chr17-41620714-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_000422.3(KRT17):c.1126C>T(p.Arg376Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,612,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R376Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

KRT17
NM_000422.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0190

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34323806).

BP6

Variant 17-41620714-G-A is Benign according to our data. Variant chr17-41620714-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1090362.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1126C>T	p.Arg376Trp	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.1126C>T	p.Arg376Trp	missense_variant	6/8	1	NM_000422.3	P1
KRT17	ENST00000648859.1 linkuse as main transcript	c.118C>T	p.Arg40Trp	missense_variant	1/2
KRT17	ENST00000493253.5 linkuse as main transcript	n.1513C>T		non_coding_transcript_exon_variant	5/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.402C>T		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000877

AC:

AN:

250738

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.0000815

AC:

119

AN:

1459908

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000782

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000889

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000109

EpiControl

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

Mar 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;D;D

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.14

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.4

M;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.71

Polyphen

0.25

B;B;.

Vest4

0.90, 0.86

MVP

0.95

MPC

0.43

ClinPred

0.31

GERP RS

-0.78

Varity_R

0.62

gMVP

0.74

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