Variant chr21-44600767-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198689.3(KRTAP10-7):c.146C>T(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000482 in 1,598,234 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000038 ( 2 hom. )

Consequence

KRTAP10-7
NM_198689.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

Variant links:

Genes affected

KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP10-7 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.16959992).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTAP10-7	NM_198689.3 linkuse as main transcript	c.146C>T	p.Pro49Leu	missense_variant	1/1	ENST00000609664.2
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-32762G>A		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-32762G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-7	ENST00000609664.2 linkuse as main transcript	c.146C>T	p.Pro49Leu	missense_variant	1/1		NM_198689.3	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-32762G>A		intron_variant		1	NM_144991.3	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*28-32762G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000150

AC:

AN:

146584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000593

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000286

AC:

AN:

210054

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

114246

show subpopulations

Gnomad AFR exome

AF:

0.0000795

Gnomad AMR exome

AF:

0.0000963

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000215

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1451650

Hom.:

Cov.:

AF XY:

0.0000346

AC XY:

AN XY:

721984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000930

Gnomad4 AMR exome

AF:

0.000584

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.000150

AC:

AN:

146584

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

71612

show subpopulations

Gnomad4 AFR

AF:

0.0000531

Gnomad4 AMR

AF:

0.00107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000593

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000151

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

Jan 24, 2024

The c.146C>T (p.P49L) alteration is located in exon 1 (coding exon 1) of the KRTAP10-7 gene. This alteration results from a C to T substitution at nucleotide position 146, causing the proline (P) at amino acid position 49 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

0.11

Eigen_PC

Benign

0.041

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.70

M_CAP

Benign

0.0033

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

D;D

Sift4G

Pathogenic

0.0

Vest4

0.22

MVP

0.67

ClinPred

0.45

GERP RS

3.9

Varity_R

0.13

gMVP

0.071

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