NM_003492.3:c.209C>G

Variant names:

• chrX-153982271-C-G
• rs2266890
• NM_003492.3:c.209C>G

Variant summary

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

The NM_003492.3(TMEM187):​c.209C>G​(p.Ser70Trp) 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. 15/21 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: 1.78
• Publications: 23 publications found

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

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=0.11855957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	NM_003492.3	MANE Select	c.209C>G	p.Ser70Trp	missense	Exon 2 of 2	NP_003483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.209C>G	p.Ser70Trp	missense	Exon 2 of 2	ENSP00000358999.4
	TMEM187	ENST00000425274.1	TSL:5	c.*11C>G		downstream_gene	N/A	ENSP00000390108.1
	TMEM187	ENST00000431598.1	TSL:3	c.*110C>G		downstream_gene	N/A	ENSP00000412872.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 14636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.0054	T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	2.8	N
REVEL	Benign	0.086
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.041	B
Vest4		0.19
MutPred		0.30		Gain of MoRF binding (P = 0.0365)
MVP		0.17
MPC		0.22
ClinPred		0.19	T
GERP RS		0.24
Varity_R		0.088
gMVP		0.73
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2266890; hg19: chrX-153247722;