Genetic Variant KRTAP17-1:p.Gly44Val (chr17-41315520-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031964.2(KRTAP17-1):c.131G>T(p.Gly44Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000621 in 1,449,832 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

KRTAP17-1
NM_031964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

KRTAP17-1 (HGNC:18917): (keratin associated protein 17-1) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

KRTAP17-1 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.30565196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP17-1	NM_031964.2 link	c.131G>T	p.Gly44Val	missense_variant	Exon 1 of 1	ENST00000334202.5	NP_114170.1	Q9BYP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP17-1	ENST00000334202.5 link	c.131G>T	p.Gly44Val	missense_variant	Exon 1 of 1	6	NM_031964.2	ENSP00000333993.3		Q9BYP8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

225954

Hom.:

AF XY:

0.0000324

AC XY:

AN XY:

123376

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000404

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000621

AC:

AN:

1449832

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720542

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000633

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.131G>T (p.G44V) alteration is located in exon 1 (coding exon 1) of the KRTAP17-1 gene. This alteration results from a G to T substitution at nucleotide position 131, causing the glycine (G) at amino acid position 44 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0069

Eigen

Benign

0.023

Eigen_PC

Benign

-0.096

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.085

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

3.6

REVEL

Uncertain

0.36

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.41

MutPred

0.23

Gain of sheet (P = 0.0101);

MVP

0.58

MPC

0.29

ClinPred

0.22

GERP RS

4.0

Varity_R

0.17

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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