rs781946877

Variant names:

• chrX-153982190-C-A
• rs781946877
• NM_003492.3:c.128C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153982190-C-A
• chrX-153982190-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003492.3(TMEM187):​c.128C>A​(p.Ala43Glu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A43V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046334654).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	NM_003492.3	MANE Select	c.128C>A	p.Ala43Glu	missense	Exon 2 of 2	NP_003483.1	Q14656

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.128C>A	p.Ala43Glu	missense	Exon 2 of 2	ENSP00000358999.4	Q14656
	TMEM187	ENST00000855602.1		c.128C>A	p.Ala43Glu	missense	Exon 2 of 2	ENSP00000525661.1
	TMEM187	ENST00000855603.1		c.128C>A	p.Ala43Glu	missense	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.74
DEOGEN2	Benign	0.0098	T
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.21
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.036
Sift	Benign	0.68	T
Sift4G	Benign	0.96	T
Polyphen		0.61	P
Vest4		0.21
MutPred		0.33		Gain of solvent accessibility (P = 0.0145)
MVP		0.076
MPC		0.47
ClinPred		0.15	T
GERP RS		-0.32
Varity_R		0.059
gMVP		0.24
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: rs781946877; hg19: chrX-153247641;