chr15-37936327-G-A

Position:

• chr15-37936327-G-A

Variant summary

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

The NM_152453.4(TMCO5A):​c.4G>A​(p.Glu2Lys) 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: 32)
• Consequence: TMCO5A NM_152453.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

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.4G>A	p.Glu2Lys	missense_variant	3/12	ENST00000319669.5	NP_689666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO5A	ENST00000319669.5	c.4G>A	p.Glu2Lys	missense_variant	3/12	1	NM_152453.4	ENSP00000327234	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 13, 2023

The c.4G>A (p.E2K) alteration is located in exon 2 (coding exon 1) of the TMCO5A gene. This alteration results from a G to A substitution at nucleotide position 4, causing the glutamic acid (E) at amino acid position 2 to be replaced by a lysine (K). 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	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.;.;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.52	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Uncertain	-0.0083	T
MutationAssessor	Uncertain	2.5	.;.;M;.;.;M
MutationTaster	Benign	0.67	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0, 1.0	.;.;D;.;.;D
Vest4		0.68, 0.68, 0.69
MutPred		0.28		Gain of MoRF binding (P = 0.1258);Gain of MoRF binding (P = 0.1258);Gain of MoRF binding (P = 0.1258);Gain of MoRF binding (P = 0.1258);Gain of MoRF binding (P = 0.1258);Gain of MoRF binding (P = 0.1258);
MVP		0.081
MPC		0.46
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.60

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: chr15-38228528; COSMIC: COSV100148767;