chr15-37941161-C-A

Position:

• chr15-37941161-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152453.4(TMCO5A):​c.400C>A​(p.Gln134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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: 1.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07299197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO5A	NM_152453.4	c.400C>A	p.Gln134Lys	missense_variant	7/12	ENST00000319669.5	NP_689666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO5A	ENST00000319669.5	c.400C>A	p.Gln134Lys	missense_variant	7/12	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

Jun 21, 2022

The c.400C>A (p.Q134K) alteration is located in exon 6 (coding exon 5) of the TMCO5A gene. This alteration results from a C to A substitution at nucleotide position 400, causing the glutamine (Q) at amino acid position 134 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	Benign	0.087
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.017	T;.;T;T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;L
MutationTaster	Benign	0.60	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.46	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.77	T;T;T;T
Sift4G	Benign	0.099	T;T;T;T
Polyphen		0.78, 0.57	.;P;.;P
Vest4		0.40, 0.40, 0.40
MutPred		0.23		Gain of ubiquitination at Q134 (P = 0.0114);Gain of ubiquitination at Q134 (P = 0.0114);Gain of ubiquitination at Q134 (P = 0.0114);Gain of ubiquitination at Q134 (P = 0.0114);
MVP		0.17
MPC		0.12
ClinPred		0.35	T
GERP RS		5.3
Varity_R		0.17
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr15-38233362;