7-36334072-G-C

Variant summary

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

The NM_001199706.2(MATCAP2):ā€‹c.1081C>Gā€‹(p.Pro361Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., cov: 31)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

MATCAP2
NM_001199706.2 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.45
Variant links:
Genes affected
MATCAP2 (HGNC:22206): (microtubule associated tyrosine carboxypeptidase 2)

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/exons MANE Protein UniProt
MATCAP2NM_001199706.2 linkuse as main transcriptc.1081C>G p.Pro361Ala missense_variant 5/7 ENST00000440378.6 NP_001186635.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MATCAP2ENST00000440378.6 linkuse as main transcriptc.1081C>G p.Pro361Ala missense_variant 5/71 NM_001199706.2 ENSP00000390837 P1Q8NCT3-6

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152146
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
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:
0.00
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
249474
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135352
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000869
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:
0.00
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461828
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000246
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:
0.00
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152146
Hom.:
0
Cov.:
31
AF XY:
0.000202
AC XY:
15
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.000529
ESP6500AA
AF:
0.000782
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000497
AC:
6

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 submitterclinical testingAmbry GeneticsApr 23, 2024The c.1090C>G (p.P364A) alteration is located in exon 5 (coding exon 5) of the KIAA0895 gene. This alteration results from a C to G substitution at nucleotide position 1090, causing the proline (P) at amino acid position 364 to be replaced by an alanine (A). 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
Pathogenic
0.80
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.;.;.;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.48
T;T;T;T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.6
M;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-6.3
D;D;D;D;D;D
REVEL
Benign
0.28
Sift
Benign
0.061
T;T;T;T;D;D
Sift4G
Uncertain
0.057
T;T;T;T;T;T
Polyphen
1.0
D;D;D;.;.;.
Vest4
0.78
MVP
0.56
MPC
0.93
ClinPred
0.30
T
GERP RS
3.9
Varity_R
0.30
gMVP
0.67

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.

Other links and lift over

dbSNP: rs372968725; hg19: chr7-36373681; API