Genetic Variant NM_001040715.2:c.1309G>A (chr16-67176918-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040715.2(MATCAP1):c.1309G>A(p.Val437Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MATCAP1
NM_001040715.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

Variant links:

Genes affected

MATCAP1 (HGNC:34408): (microtubule associated tyrosine carboxypeptidase 1)

MATCAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATCAP1	NM_001040715.2 link	c.1309G>A	p.Val437Met	missense_variant	Exon 7 of 7	ENST00000563902.2	NP_001035805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATCAP1	ENST00000563902.2 link	c.1309G>A	p.Val437Met	missense_variant	Exon 7 of 7	1	NM_001040715.2	ENSP00000456838.1		Q68EN5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456114

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000602

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1309G>A (p.V437M) alteration is located in exon 7 (coding exon 6) of the KIAA0895L gene. This alteration results from a G to A substitution at nucleotide position 1309, causing the valine (V) at amino acid position 437 to be replaced by a methionine (M). 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

0.32

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.97

.;D

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.18

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;D

Vest4

0.24

MutPred

0.58

Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);

MVP

0.38

MPC

2.0

ClinPred

0.94

GERP RS

3.6

Varity_R

0.14

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over