rs6571303

chrX-153982503-C-GchrX-153982503-C-T

Variant summary

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

The NM_003492.3(TMEM187):c.441C>G(p.Cys147Trp) 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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

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=0.1735613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.441C>G	p.Cys147Trp	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.441C>G	p.Cys147Trp	missense_variant	2/2	1	NM_003492.3	P1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.2
Dann	Benign	0.84
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.32
MutPred		0.48		Gain of helix (P = 0.0425);
MVP		0.11
MPC		0.70
ClinPred		0.76	D
GERP RS		-4.6
Varity_R		0.18
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs6571303; hg19: chrX-153247954;