Variant 17-41097861-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031960.3(KRTAP4-8):c.224G>T(p.Cys75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,516,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

KRTAP4-8
NM_031960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.195

Variant links:

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP4-8 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=0.38011116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP4-8	NM_031960.3 linkuse as main transcript	c.224G>T	p.Cys75Phe	missense_variant	1/1	ENST00000333822.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP4-8	ENST00000333822.5 linkuse as main transcript	c.224G>T	p.Cys75Phe	missense_variant	1/1		NM_031960.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000334

AC:

AN:

149764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

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:

0.0000593

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1366272

Hom.:

Cov.:

160

AF XY:

0.0000237

AC XY:

AN XY:

675430

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:

0.0000322

Gnomad4 OTH exome

AF:

0.0000359

GnomAD4 genome

AF:

0.0000334

AC:

AN:

149764

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73002

show subpopulations

Gnomad4 AFR

AF:

0.0000247

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:

0.0000593

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000954

Hom.:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.224G>T (p.C75F) alteration is located in exon 1 (coding exon 1) of the KRTAP4-8 gene. This alteration results from a G to T substitution at nucleotide position 224, causing the cysteine (C) at amino acid position 75 to be replaced by a phenylalanine (F). 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

Benign

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.59

M_CAP

Benign

0.0030

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

4.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.17

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.38

MVP

0.21

MPC

0.14

ClinPred

0.98

GERP RS

3.7

Varity_R

0.66

gMVP

0.10

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