Variant 21-30396367-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181599.3(KRTAP13-1):c.281C>A(p.Thr94Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KRTAP13-1
NM_181599.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.219

Variant links:

Genes affected

KRTAP13-1 (HGNC:18924): (keratin associated protein 13-1) Hair keratins and hair keratin-associated proteins (KAPs), such as KRTAP13-1, are the main structural proteins of hair fibers (Rogers et al., 2002 [PubMed 12359730]).[supplied by OMIM, Mar 2008]

KRTAP13-1 links:

LOC105372772 (HGNC:):

LOC105372772 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25125623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP13-1	NM_181599.3 linkuse as main transcript	c.281C>A	p.Thr94Lys	missense_variant	1/1	ENST00000355459.4	NP_853630.2
LOC105372772	XR_937653.3 linkuse as main transcript	n.196-3007G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP13-1	ENST00000355459.4 linkuse as main transcript	c.281C>A	p.Thr94Lys	missense_variant	1/1		NM_181599.3	ENSP00000347635	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000113

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 18, 2023

The c.281C>A (p.T94K) alteration is located in exon 1 (coding exon 1) of the KRTAP13-1 gene. This alteration results from a C to A substitution at nucleotide position 281, causing the threonine (T) at amino acid position 94 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.024

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.68

M_CAP

Benign

0.0061

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.048

Sift

Uncertain

0.027

Sift4G

Uncertain

0.059

Polyphen

0.99

Vest4

0.24

MutPred

0.36

Gain of methylation at T94 (P = 0.0131);

MVP

0.34

MPC

0.29

ClinPred

0.64

GERP RS

0.56

Varity_R

0.20

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