16-67178276-C-A

Variant names:

• chr16-67178276-C-A
• rs1290361199
• NM_001040715.2:c.1076G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040715.2(MATCAP1):​c.1076G>T​(p.Arg359Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R359H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MATCAP1 NM_001040715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31408235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040715.2. 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
	MATCAP1	NM_001040715.2	MANE Select	c.1076G>T	p.Arg359Leu	missense	Exon 5 of 7	NP_001035805.1	Q68EN5-1
	MATCAP1	NM_001369680.1		c.1076G>T	p.Arg359Leu	missense	Exon 6 of 8	NP_001356609.1	Q68EN5-1
	MATCAP1	NM_001369681.1		c.1076G>T	p.Arg359Leu	missense	Exon 6 of 8	NP_001356610.1	Q68EN5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATCAP1	ENST00000563902.2	TSL:1 MANE Select	c.1076G>T	p.Arg359Leu	missense	Exon 5 of 7	ENSP00000456838.1	Q68EN5-1
	MATCAP1	ENST00000561621.5	TSL:1	c.1076G>T	p.Arg359Leu	missense	Exon 6 of 8	ENSP00000457099.1	Q68EN5-2
	MATCAP1	ENST00000290881.11	TSL:5	c.1076G>T	p.Arg359Leu	missense	Exon 6 of 8	ENSP00000290881.7	Q68EN5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1419910 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 702634

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 38626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25434

East Asian (EAS) AF: 0.00 AC: 0 AN: 37052

South Asian (SAS) AF: 0.00 AC: 0 AN: 81092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091364

Other (OTH) AF: 0.00 AC: 0 AN: 58822

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.00090	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.14
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.89	P
Vest4		0.50
MutPred		0.48		Loss of helix (P = 0.0093)
MVP		0.30
MPC		1.6
ClinPred		0.99	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.61
Mutation Taster		=63/37	polymorphism

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: rs1290361199; hg19: chr16-67212179;