NM_001040715.2:c.1114G>T

Variant names:

• chr16-67178238-C-A
• rs1370496881
• NM_001040715.2:c.1114G>T

Variant summary

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

The NM_001040715.2(MATCAP1):​c.1114G>T​(p.Val372Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V372M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MATCAP1 NM_001040715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• 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.1114G>T	p.Val372Leu	missense	Exon 5 of 7	NP_001035805.1	Q68EN5-1
	MATCAP1	NM_001369680.1		c.1114G>T	p.Val372Leu	missense	Exon 6 of 8	NP_001356609.1	Q68EN5-1
	MATCAP1	NM_001369681.1		c.1114G>T	p.Val372Leu	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.1114G>T	p.Val372Leu	missense	Exon 5 of 7	ENSP00000456838.1	Q68EN5-1
	MATCAP1	ENST00000561621.5	TSL:1	c.1114G>T	p.Val372Leu	missense	Exon 6 of 8	ENSP00000457099.1	Q68EN5-2
	MATCAP1	ENST00000290881.11	TSL:5	c.1114G>T	p.Val372Leu	missense	Exon 6 of 8	ENSP00000290881.7	Q68EN5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400374 Hom.: 0 Cov.: 36 AF XY: 0.00000145 AC XY: 1 AN XY: 690418

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32016

American (AMR) AF: 0.00 AC: 0 AN: 36140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24816

East Asian (EAS) AF: 0.00 AC: 0 AN: 36328

South Asian (SAS) AF: 0.00 AC: 0 AN: 79986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079426

Other (OTH) AF: 0.00 AC: 0 AN: 57878

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0021	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.091
Sift	Benign	0.21	T
Sift4G	Benign	0.28	T
Polyphen		0.87	P
Vest4		0.34
MutPred		0.56		Loss of sheet (P = 0.007)
MVP		0.47
MPC		1.6
ClinPred		0.74	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.55

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: rs1370496881; hg19: chr16-67212141;