X-153982220-C-T

Position:

• chrX-153982220-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.158C>T​(p.Ala53Val) 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. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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=0.24315682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3	c.158C>T	p.Ala53Val	missense_variant	2/2	ENST00000369982.5	NP_003483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM187	ENST00000369982.5	c.158C>T	p.Ala53Val	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4
TMEM187	ENST00000425274.1	c.158C>T	p.Ala53Val	missense_variant	2/2	5		ENSP00000390108.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

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

Sep 04, 2024

The c.158C>T (p.A53V) alteration is located in exon 2 (coding exon 1) of the TMEM187 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the alanine (A) at amino acid position 53 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.13
Sift	Benign	0.14	T;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.87	P;.
Vest4		0.16
MutPred		0.30		Gain of catalytic residue at A53 (P = 0.1049);Gain of catalytic residue at A53 (P = 0.1049);
MVP		0.24
MPC		0.29
ClinPred		0.83	D
GERP RS		2.5
Varity_R		0.13
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153247671;