rs13397

Variant names:

• chrX-153982797-G-A
• rs13397
• NM_003492.3:c.735G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 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: Benign. The variant received -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.

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.735G>A	p.Thr245Thr	synonymous	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.735G>A	p.Thr245Thr	synonymous	Exon 2 of 2	ENSP00000358999.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 18006 AN: 111756 Hom.: 1826 Cov.: 24

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

GnomAD2 exomes AF: 0.273 AC: 49859 AN: 182794 AF XY: 0.274

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 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

African (AFR) AF: 0.0353 AC: 931 AN: 26402

American (AMR) AF: 0.475 AC: 16683 AN: 35146

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 5224 AN: 19384

East Asian (EAS) AF: 0.686 AC: 20727 AN: 30200

South Asian (SAS) AF: 0.526 AC: 28493 AN: 54144

European-Finnish (FIN) AF: 0.134 AC: 5413 AN: 40503

Middle Eastern (MID) AF: 0.360 AC: 1488 AN: 4135

European-Non Finnish (NFE) AF: 0.124 AC: 104818 AN: 842050

Other (OTH) AF: 0.222 AC: 10222 AN: 46089

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

African (AFR) AF: 0.0400 AC: 1236 AN: 30917

American (AMR) AF: 0.363 AC: 3821 AN: 10516

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 639 AN: 2630

East Asian (EAS) AF: 0.687 AC: 2400 AN: 3492

South Asian (SAS) AF: 0.539 AC: 1440 AN: 2671

European-Finnish (FIN) AF: 0.130 AC: 789 AN: 6064

Middle Eastern (MID) AF: 0.301 AC: 65 AN: 216

European-Non Finnish (NFE) AF: 0.137 AC: 7254 AN: 53088

Other (OTH) AF: 0.217 AC: 333 AN: 1533

Alfa AF: 0.167 Hom.: 8678

Bravo AF: 0.178

EpiCase AF: 0.153

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.079
DANN	Benign	0.92
PhyloP100		-4.3
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13397; hg19: chrX-153248248; COSMIC: COSV64141113; COSMIC: COSV64141113;