Variant 17-41227028-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031961.3(KRTAP9-2):c.374C>G(p.Thr125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP9-2
NM_031961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

Variant links:

Genes affected

KRTAP9-2 (HGNC:16926): (keratin associated protein 9-2) 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]

KRTAP9-2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0327757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP9-2	NM_031961.3 linkuse as main transcript	c.374C>G	p.Thr125Ser	missense_variant	1/1	ENST00000377721.3	NP_114167.2	Q9BYQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP9-2	ENST00000377721.3 linkuse as main transcript	c.374C>G	p.Thr125Ser	missense_variant	1/1	6	NM_031961.3	ENSP00000366950.3		Q9BYQ4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

174

AN:

151922

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000211

AC:

AN:

251448

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000579

AC:

846

AN:

1460482

Hom.:

Cov.:

208

AF XY:

0.000539

AC XY:

392

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000824

Gnomad4 NFE exome

AF:

0.000665

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00114

AC:

174

AN:

152040

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00211

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000578

Hom.:

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

Mar 14, 2023

The c.374C>G (p.T125S) alteration is located in exon 1 (coding exon 1) of the KRTAP9-2 gene. This alteration results from a C to G substitution at nucleotide position 374, causing the threonine (T) at amino acid position 125 to be replaced by a serine (S). 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

0.088

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.17

DANN

Benign

0.30

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00011

LIST_S2

Benign

0.012

M_CAP

Benign

0.0021

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.36

REVEL

Benign

0.020

Sift

Benign

0.52

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.14

MutPred

0.52

Loss of sheet (P = 0.0181);

MVP

0.12

MPC

1.4

ClinPred

0.0084

GERP RS

0.77

Varity_R

0.023

gMVP

0.032

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