Variant chr21-44574089-G-A 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_198687.2(KRTAP10-4):c.331G>A(p.Val111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 142,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP10-4
NM_198687.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]

KRTAP10-4 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:

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=0.008329302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-4	NM_198687.2 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	1/1	ENST00000400374.4
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-6084C>T		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-6084C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-4	ENST00000400374.4 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	1/1		NM_198687.2	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-6084C>T		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*28-6084C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

219

AN:

142048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000483

Gnomad ASJ

AF:

0.000915

Gnomad EAS

AF:

0.00471

Gnomad SAS

AF:

0.00297

Gnomad FIN

AF:

0.000794

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000460

Gnomad OTH

AF:

0.00158

GnomAD3 exomes

AF:

0.000133

AC:

AN:

248622

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000606

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000123

AC:

177

AN:

1443908

Hom.:

Cov.:

174

AF XY:

0.000128

AC XY:

AN XY:

718024

show subpopulations

Gnomad4 AFR exome

AF:

0.000556

Gnomad4 AMR exome

AF:

0.000318

Gnomad4 ASJ exome

AF:

0.000117

Gnomad4 EAS exome

AF:

0.000527

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000898

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.00155

AC:

220

AN:

142132

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

115

AN XY:

69264

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.000483

Gnomad4 ASJ

AF:

0.000915

Gnomad4 EAS

AF:

0.00473

Gnomad4 SAS

AF:

0.00297

Gnomad4 FIN

AF:

0.000794

Gnomad4 NFE

AF:

0.000460

Gnomad4 OTH

AF:

0.00209

Alfa

AF:

0.0119

Hom.:

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

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

Jun 24, 2022

The c.331G>A (p.V111M) alteration is located in exon 1 (coding exon 1) of the KRTAP10-4 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.13

T;.

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.034

Sift

Benign

0.12

.;T

Sift4G

Benign

0.11

.;T

Vest4

0.15

MVP

0.085

MPC

0.45

ClinPred

0.013

GERP RS

-4.4

gMVP

0.051

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