rs770872373

Variant names:

• chr16-67178018-G-T
• rs770872373
• NM_001040715.2:c.1243C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-67178018-G-T
• chr16-67178018-G-C

Variant summary

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

The NM_001040715.2(MATCAP1):​c.1243C>A​(p.Leu415Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: MATCAP1 NM_001040715.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70
• Publications: 0 publications found

Genes affected

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

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_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.1243C>A	p.Leu415Met	missense	Exon 6 of 7	NP_001035805.1	Q68EN5-1
	MATCAP1	NM_001369680.1		c.1243C>A	p.Leu415Met	missense	Exon 7 of 8	NP_001356609.1	Q68EN5-1
	MATCAP1	NM_001369681.1		c.1243C>A	p.Leu415Met	missense	Exon 7 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.1243C>A	p.Leu415Met	missense	Exon 6 of 7	ENSP00000456838.1	Q68EN5-1
	MATCAP1	ENST00000561621.5	TSL:1	c.*6C>A		3_prime_UTR	Exon 7 of 8	ENSP00000457099.1	Q68EN5-2
	MATCAP1	ENST00000290881.11	TSL:5	c.1243C>A	p.Leu415Met	missense	Exon 7 of 8	ENSP00000290881.7	Q68EN5-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152278 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248908 AF XY: 0.0000222

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1461676 Hom.: 0 Cov.: 32 AF XY: 0.0000591 AC XY: 43 AN XY: 727154

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000791 AC: 88 AN: 1111878

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74396

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000827 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.35
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.22
Sift	Benign	0.063	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.72		Loss of catalytic residue at L415 (P = 0.011)
MVP		0.38
MPC		2.0
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.29
gMVP		0.47
Mutation Taster		=83/17	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: rs770872373; hg19: chr16-67211921;