Variant 21-44580407-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_198694.3(KRTAP10-5):c.172C>T(p.Pro58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 1,613,066 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 87 hom. )

Consequence

KRTAP10-5
NM_198694.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.498

Variant links:

Genes affected

KRTAP10-5 (HGNC:22969): (keratin associated protein 10-5) 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]

KRTAP10-5 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 -6 ACMG points.

BP6

Variant 21-44580407-G-A is Benign according to our data. Variant chr21-44580407-G-A is described in ClinVar as [Benign]. Clinvar id is 2652767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-5	NM_198694.3 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/1	ENST00000400372.1	NP_941967.3	P60370
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-12402C>T		intron_variant		ENST00000323084.9	NP_659428.2	Q8WU66-1
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-12402C>T		intron_variant			NP_001258966.1	Q8WU66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP10-5	ENST00000400372.1 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/1	6	NM_198694.3	ENSP00000383223.1	P60370
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-12402C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	n.*28-12402C>T		intron_variant				ENSP00000496535.1	A0A2R8YFK6

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1152

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00780

AC:

1937

AN:

248276

Hom.:

AF XY:

0.00782

AC XY:

1055

AN XY:

134876

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.00603

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.00631

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.00992

AC:

14496

AN:

1460730

Hom.:

Cov.:

135

AF XY:

0.00986

AC XY:

7167

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00255

Gnomad4 FIN exome

AF:

0.00538

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00755

AC:

1150

AN:

152336

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

556

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00594

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00766

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00251

AC:

ESP6500EA

AF:

0.00875

AC:

ExAC

AF:

0.00758

AC:

919

EpiCase

AF:

0.0128

EpiControl

AF:

0.0130

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

Oct 01, 2023

KRTAP10-5: BP4, BS1, BS2; TSPEAR: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.62

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0046

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.027

Sift

Benign

0.14

Sift4G

Benign

0.095

Vest4

0.079

MVP

0.030

MPC

0.031

ClinPred

0.0044

GERP RS

-3.4

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: 6

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