Variant 17-41620876-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.964G>A(p.Ala322Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,614,010 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00088 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

KRT17
NM_000422.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

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=0.02998215).

BP6

Variant 17-41620876-C-T is Benign according to our data. Variant chr17-41620876-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2065609.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000879 (134/152370) while in subpopulation AFR AF= 0.00308 (128/41588). AF 95% confidence interval is 0.00264. There are 2 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	6/8	ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	6/8	1	NM_000422.3	ENSP00000308452	P1
KRT17	ENST00000493253.5 linkuse as main transcript	n.1351G>A		non_coding_transcript_exon_variant	5/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.240G>A		non_coding_transcript_exon_variant	2/4
KRT17	ENST00000648859.1 linkuse as main transcript			upstream_gene_variant				ENSP00000497161

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000167

AC:

AN:

250944

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000883

AC:

129

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000879

AC:

134

AN:

152370

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000937

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 02, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;D;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.74

.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Uncertain

0.025

MutationAssessor

Uncertain

2.3

M;M;.

MutationTaster

Benign

0.94

N;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

.;N;.

REVEL

Uncertain

0.59

Sift

Benign

0.18

.;T;.

Sift4G

Benign

0.39

.;T;T

Polyphen

0.87

P;P;.

Vest4

0.57, 0.57

MVP

0.94

MPC

0.37

ClinPred

0.046

GERP RS

3.0

Varity_R

0.21

gMVP

0.48

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