Variant 17-41226911-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031961.3(KRTAP9-2):c.257G>A(p.Cys86Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

KRTAP9-2
NM_031961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP9-2	NM_031961.3 linkuse as main transcript	c.257G>A	p.Cys86Tyr	missense_variant	1/1	ENST00000377721.3	NP_114167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP9-2	ENST00000377721.3 linkuse as main transcript	c.257G>A	p.Cys86Tyr	missense_variant	1/1		NM_031961.3	ENSP00000366950	P1

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

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:

0.00342

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250508

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135592

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461778

Hom.:

Cov.:

207

AF XY:

0.0000344

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150686

Hom.:

Cov.:

AF XY:

0.0000679

AC XY:

AN XY:

73646

show subpopulations

Gnomad4 AFR

AF:

0.0000733

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:

0.0000591

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

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

May 27, 2022

The c.257G>A (p.C86Y) alteration is located in exon 1 (coding exon 1) of the KRTAP9-2 gene. This alteration results from a G to A substitution at nucleotide position 257, causing the cysteine (C) at amino acid position 86 to be replaced by a tyrosine (Y). 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

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.53

M_CAP

Benign

0.0072

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-9.4

REVEL

Benign

0.21

Sift

Benign

0.042

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.35

MutPred

0.75

Gain of sheet (P = 0.1208);

MVP

0.31

MPC

1.8

ClinPred

0.99

GERP RS

3.5

Varity_R

0.66

gMVP

0.17

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