16-67178238-C-T

Variant names:

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

Variant summary

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

The NM_001040715.2(MATCAP1):​c.1114G>A​(p.Val372Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MATCAP1 NM_001040715.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

Genes affected

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

ACMG classification

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 rank	MANE	Protein	UniProt
MATCAP1	NM_001040715.2	c.1114G>A	p.Val372Met	missense_variant	Exon 5 of 7	ENST00000563902.2	NP_001035805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATCAP1	ENST00000563902.2	c.1114G>A	p.Val372Met	missense_variant	Exon 5 of 7	1	NM_001040715.2	ENSP00000456838.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1400374 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 690418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114G>A (p.V372M) alteration is located in exon 5 (coding exon 4) of the KIAA0895L gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the valine (V) at amino acid position 372 to be replaced by a methionine (M). 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	Uncertain	0.40
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.0082	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.061	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.48
MutPred		0.51		Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP		0.53
MPC		2.1
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.50

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

Other links and lift over

dbSNP: rs1370496881; hg19: chr16-67212141;