chr15-37941693-T-G

Position:

• chr15-37941693-T-G

Variant summary

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

The NM_152453.4(TMCO5A):​c.467T>G​(p.Val156Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMCO5A NM_152453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

Genes affected

TMCO5A (HGNC:28558): (transmembrane and coiled-coil domains 5A) Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
TMCO5A	NM_152453.4	c.467T>G	p.Val156Gly	missense_variant	8/12	ENST00000319669.5	NP_689666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO5A	ENST00000319669.5	c.467T>G	p.Val156Gly	missense_variant	8/12	1	NM_152453.4	ENSP00000327234	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.467T>G (p.V156G) alteration is located in exon 7 (coding exon 6) of the TMCO5A gene. This alteration results from a T to G substitution at nucleotide position 467, causing the valine (V) at amino acid position 156 to be replaced by a glycine (G). 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	0.58
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	2.9	M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.62
MutPred		0.55		Loss of stability (P = 0.04);Loss of stability (P = 0.04);Loss of stability (P = 0.04);
MVP		0.10
MPC		0.49
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.69
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr15-38233894;