7-36335078-T-C

Variant names:

• chr7-36335078-T-C
• rs369747082
• NM_001199706.2:c.959A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001199706.2(MATCAP2):​c.959A>G​(p.His320Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,550 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: 0.0000014 (0 hom.)
• Consequence: MATCAP2 NM_001199706.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58
• Publications: 0 publications found

Genes affected

MATCAP2 (HGNC:22206): (microtubule associated tyrosine carboxypeptidase 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199706.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATCAP2	NM_001199706.2	MANE Select	c.959A>G	p.His320Arg	missense	Exon 4 of 7	NP_001186635.1	Q8NCT3-6
	MATCAP2	NM_001100425.2		c.968A>G	p.His323Arg	missense	Exon 4 of 7	NP_001093895.1	Q8NCT3-1
	MATCAP2	NM_001199707.2		c.929A>G	p.His310Arg	missense	Exon 3 of 6	NP_001186636.1	Q8NCT3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATCAP2	ENST00000440378.6	TSL:1 MANE Select	c.959A>G	p.His320Arg	missense	Exon 4 of 7	ENSP00000390837.1	Q8NCT3-6
	MATCAP2	ENST00000297063.10	TSL:1	c.968A>G	p.His323Arg	missense	Exon 4 of 7	ENSP00000297063.6	Q8NCT3-1
	MATCAP2	ENST00000338533.9	TSL:1	c.929A>G	p.His310Arg	missense	Exon 3 of 6	ENSP00000344805.5	Q8NCT3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461550 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727048

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111874

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.23
Sift	Benign	0.049	D
Sift4G	Uncertain	0.051	T
Polyphen		0.98	D
Vest4		0.76
MVP		0.51
MPC		0.40
ClinPred		0.65	D
GERP RS		5.8
Varity_R		0.56
gMVP		0.68
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs369747082; hg19: chr7-36374687;