Variant 21-44666553-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_181684.3(KRTAP12-2):c.334C>T(p.Pro112Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,600,000 control chromosomes in the GnomAD database, including 62 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 59 hom. )

Consequence

KRTAP12-2
NM_181684.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

KRTAP12-2 (HGNC:20530): (keratin associated protein 12-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP12-2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008563906).

BP6

Variant 21-44666553-G-A is Benign according to our data. Variant chr21-44666553-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652780.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP12-2	NM_181684.3 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	1/1	ENST00000360770.3	NP_859012.1	P59991
TSPEAR	NM_144991.3 linkuse as main transcript	c.82+44880C>T		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-123+23992C>T		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP12-2	ENST00000360770.3 linkuse as main transcript	c.334C>T	p.Pro112Ser	missense_variant	1/1	6	NM_181684.3	ENSP00000354001.3	P59991
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.82+44880C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*27+23992C>T		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

707

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00354

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00408

AC:

1018

AN:

249216

Hom.:

AF XY:

0.00422

AC XY:

570

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00577

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00624

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.00755

AC:

10925

AN:

1447854

Hom.:

Cov.:

101

AF XY:

0.00747

AC XY:

5378

AN XY:

720410

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00579

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00407

Gnomad4 FIN exome

AF:

0.000528

Gnomad4 NFE exome

AF:

0.00891

Gnomad4 OTH exome

AF:

0.00706

GnomAD4 genome

AF:

0.00464

AC:

706

AN:

152146

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00354

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00771

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00623

Hom.:

Bravo

AF:

0.00454

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00185

AC:

ESP6500EA

AF:

0.00811

AC:

ExAC

AF:

0.00402

AC:

488

EpiCase

AF:

0.00731

EpiControl

AF:

0.00735

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

Oct 01, 2023

KRTAP12-2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

0.15

Eigen_PC

Benign

-0.031

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

M_CAP

Benign

0.011

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.31

MVP

0.44

MPC

0.76

ClinPred

0.055

GERP RS

3.5

Varity_R

0.77

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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