Variant 21-44600755-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198689.3(KRTAP10-7):c.134C>G(p.Pro45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,604,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KRTAP10-7
NM_198689.3 missense

Scores

Splicing: ADA: 0.00007296

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.79

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118919045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRTAP10-7	NM_198689.3 linkuse as main transcript	c.134C>G	p.Pro45Arg	missense_variant	1/1	ENST00000609664.2	NP_941962.1
TSPEAR	NM_144991.3 linkuse as main transcript	c.83-32750G>C		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2 linkuse as main transcript	c.-122-32750G>C		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-7	ENST00000609664.2 linkuse as main transcript	c.134C>G	p.Pro45Arg	missense_variant	1/1		NM_198689.3	ENSP00000476821	P1
TSPEAR	ENST00000323084.9 linkuse as main transcript	c.83-32750G>C		intron_variant		1	NM_144991.3	ENSP00000321987	P1	Q8WU66-1
TSPEAR	ENST00000642437.1 linkuse as main transcript	c.*28-32750G>C		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes

AF:

0.00000678

AC:

AN:

147594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000960

AC:

AN:

208260

Hom.:

AF XY:

0.00000880

AC XY:

AN XY:

113674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000765

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456462

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724440

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0000588

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000678

AC:

AN:

147594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72100

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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

Feb 17, 2022

The c.134C>G (p.P45R) alteration is located in exon 1 (coding exon 1) of the KRTAP10-7 gene. This alteration results from a C to G substitution at nucleotide position 134, causing the proline (P) at amino acid position 45 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.015

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.18

Sift4G

Uncertain

0.0040

Vest4

0.12

MutPred

0.23

Gain of solvent accessibility (P = 0.0246);

MVP

0.43

ClinPred

0.14

GERP RS

-0.74

Varity_R

0.024

gMVP

0.035

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000073

dbscSNV1_RF

Benign

0.0

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