15-37947673-G-C

Variant names:

• chr15-37947673-G-C
• rs193920912
• NM_152453.4:c.645G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152453.4(TMCO5A):​c.645G>C​(p.Lys215Asn) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMCO5A NM_152453.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.136
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07308546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO5A	NM_152453.4	c.645G>C	p.Lys215Asn	missense_variant	Exon 11 of 12	ENST00000319669.5	NP_689666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO5A	ENST00000319669.5	c.645G>C	p.Lys215Asn	missense_variant	Exon 11 of 12	1	NM_152453.4	ENSP00000327234.4
TMCO5A	ENST00000559502.5	c.645G>C	p.Lys215Asn	missense_variant	Exon 11 of 12	2		ENSP00000454112.1
TMCO5A	ENST00000560653.5	n.*85G>C		non_coding_transcript_exon_variant	Exon 11 of 12	5		ENSP00000453561.1
TMCO5A	ENST00000560653.5	n.*85G>C		3_prime_UTR_variant	Exon 11 of 12	5		ENSP00000453561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.3
DANN	Benign	0.83
DEOGEN2	Benign	0.0097	.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		0.14
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.043
Sift	Benign	0.070	T;D
Sift4G	Benign	0.085	T;T
Polyphen		0.087	B;B
Vest4		0.29
MutPred		0.32		Loss of methylation at K215 (P = 0.0032);Loss of methylation at K215 (P = 0.0032);
MVP		0.076
MPC		0.094
ClinPred		0.055	T
GERP RS		-0.40
Varity_R		0.089
gMVP		0.15

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

Other links and lift over

dbSNP: rs193920912; hg19: chr15-38239874; COSMIC: COSV60465474; COSMIC: COSV60465474;