Variant 21-44654519-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_198698.1(KRTAP12-4):c.96G>A(p.Gly32Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,613,224 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 8 hom., cov: 33)

Exomes 𝑓: 0.013 ( 159 hom. )

Consequence

KRTAP12-4
NM_198698.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.562

Variant links:

Genes affected

KRTAP12-4 (HGNC:20532): (keratin associated protein 12-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP12-4 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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 21-44654519-C-T is Benign according to our data. Variant chr21-44654519-C-T is described in ClinVar as [Benign]. Clinvar id is 2652779.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.562 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0133 (19369/1460942) while in subpopulation NFE AF= 0.0156 (17304/1111578). AF 95% confidence interval is 0.0154. There are 159 homozygotes in gnomad4_exome. There are 9279 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP12-4	NM_198698.1 linkuse as main transcript	c.96G>A	p.Gly32Gly	synonymous_variant	1/1	ENST00000391618.1	NP_941971.1	P60329
TSPEAR	NM_144991.3 linkuse as main transcript	c.82+56914G>A		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+36026G>A		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP12-4	ENST00000391618.1 linkuse as main transcript	c.96G>A	p.Gly32Gly	synonymous_variant	1/1	6	NM_198698.1	ENSP00000375476.1	P60329
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.82+56914G>A		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*27+36026G>A		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1409

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00925

AC:

2269

AN:

245172

Hom.:

AF XY:

0.00900

AC XY:

1201

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00115

Gnomad FIN exome

AF:

0.00251

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0133

AC:

19369

AN:

1460942

Hom.:

159

Cov.:

AF XY:

0.0128

AC XY:

9279

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000964

Gnomad4 FIN exome

AF:

0.00356

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.00925

AC:

1409

AN:

152282

Hom.:

Cov.:

AF XY:

0.00807

AC XY:

601

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00325

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

KRTAP12-4: BP4, BP7, BS1, BS2; TSPEAR: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.1

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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