Variant chr21-44573947-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_198687.2(KRTAP10-4):c.189G>A(p.Val63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 151,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 47)

Exomes 𝑓: 0.0013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP10-4
NM_198687.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.513

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 21-44573947-G-A is Benign according to our data. Variant chr21-44573947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652763.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.513 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-4	NM_198687.2 linkuse as main transcript	c.189G>A	p.Val63=	synonymous_variant	1/1	ENST00000400374.4
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-5942C>T		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-5942C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-4	ENST00000400374.4 linkuse as main transcript	c.189G>A	p.Val63=	synonymous_variant	1/1		NM_198687.2	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-5942C>T		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*28-5942C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

395

AN:

151132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000919

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00291

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00248

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00176

AC:

419

AN:

237396

Hom.:

AF XY:

0.00172

AC XY:

223

AN XY:

129586

show subpopulations

Gnomad AFR exome

AF:

0.0000740

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00414

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.00388

Gnomad FIN exome

AF:

0.00192

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00127

AC:

1837

AN:

1449162

Hom.:

Cov.:

164

AF XY:

0.00136

AC XY:

979

AN XY:

719696

show subpopulations

Gnomad4 AFR exome

AF:

0.00178

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00472

Gnomad4 EAS exome

AF:

0.000790

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00260

AC:

394

AN:

151252

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

187

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.00227

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00291

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00248

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00537

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

KRTAP10-4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.8

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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