Variant rs115298124 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181688.3(KRTAP10-10):c.302T>C(p.Val101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V101E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 29)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

KRTAP10-10
NM_181688.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

KRTAP10-10 (HGNC:22972): (keratin associated protein 10-10) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-10 links:

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

TSPEAR links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032742918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-10	NM_181688.3 linkuse as main transcript	c.302T>C	p.Val101Ala	missense_variant	1/1	ENST00000380095.2
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-69714A>G		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+52826A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-10	ENST00000380095.2 linkuse as main transcript	c.302T>C	p.Val101Ala	missense_variant	1/1		NM_181688.3	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-69714A>G		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*27+52826A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00000746

AC:

AN:

134064

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:

0.000269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.04e-7

AC:

AN:

1106268

Hom.:

Cov.:

110

AF XY:

0.00000183

AC XY:

AN XY:

547346

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:

0.0000171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000746

AC:

AN:

134064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65080

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:

0.000269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

Cadd

Benign

3.6

Dann

Benign

0.45

DEOGEN2

Benign

0.0091

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.028

M_CAP

Benign

0.0012

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.74

REVEL

Benign

0.016

Sift

Benign

0.10

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.084

MutPred

0.52

Gain of sheet (P = 0.1208);

MVP

0.030

MPC

0.055

ClinPred

0.083

GERP RS

-5.7

Varity_R

0.020

gMVP

0.031

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over