rs13397

Positions:

• chrX-153982797-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003492.3(TMEM187):​c.735G>A​(p.Thr245Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,209,862 control chromosomes in the GnomAD database, including 19,579 homozygotes. There are 74,890 hemizygotes in GnomAD. 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: 𝑓 0.16 (1826 hom., 5867 hem., cov: 24)
  • Exomes 𝑓: 0.18 (17753 hom. 69023 hem.)
• Consequence: TMEM187 NM_003492.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-4.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3	c.735G>A	p.Thr245Thr	synonymous_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.735G>A	p.Thr245Thr	synonymous_variant	2/2	1	NM_003492.3	ENSP00000358999.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 18006 AN: 111756 Hom.: 1826 Cov.: 24 AF XY: 0.173 AC XY: 5863 AN XY: 33964

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0381

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.273 AC: 49859 AN: 182794 Hom.: 6823 AF XY: 0.274 AC XY: 18477 AN XY: 67318

Gnomad AFR exome AF: 0.0411

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.694

Gnomad SAS exome AF: 0.533

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.177 AC: 193999 AN: 1098053 Hom.: 17753 Cov.: 33 AF XY: 0.190 AC XY: 69023 AN XY: 363427

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.161 AC: 18003 AN: 111809 Hom.: 1826 Cov.: 24 AF XY: 0.172 AC XY: 5867 AN XY: 34027

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.217

Alfa AF: 0.168 Hom.: 5324

Bravo AF: 0.178

EpiCase AF: 0.153

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.079
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13397; hg19: chrX-153248248; COSMIC: COSV64141113; COSMIC: COSV64141113;