chr16-67178247-C-G

Variant names:

• chr16-67178247-C-G
• NM_001040715.2:c.1105G>C

Variant summary

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

The NM_001040715.2(MATCAP1):​c.1105G>C​(p.Glu369Gln) 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)
• Consequence: MATCAP1 NM_001040715.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

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.1105G>C	p.Glu369Gln	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.1105G>C	p.Glu369Gln	missense_variant	Exon 5 of 7	1	NM_001040715.2	ENSP00000456838.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1105G>C (p.E369Q) alteration is located in exon 5 (coding exon 4) of the KIAA0895L gene. This alteration results from a G to C substitution at nucleotide position 1105, causing the glutamic acid (E) at amino acid position 369 to be replaced by a glutamine (Q). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.49
Sift	Benign	0.072	T;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.53
MutPred		0.54		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.48
MPC		2.0
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67212150;