X-153982503-C-T

Variant names:

• chrX-153982503-C-T
• rs6571303
• NM_003492.3:c.441C>T

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.441C>T​(p.Cys147Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,202,457 control chromosomes in the GnomAD database, including 26,626 homozygotes. There are 90,300 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 0.21 (2530 hom., 7735 hem., cov: 25)
  • Exomes 𝑓: 0.22 (24096 hom. 82565 hem.)
• Consequence: TMEM187 NM_003492.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 16 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=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	NM_003492.3	MANE Select	c.441C>T	p.Cys147Cys	synonymous	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.441C>T	p.Cys147Cys	synonymous	Exon 2 of 2	ENSP00000358999.4	Q14656
	TMEM187	ENST00000855602.1		c.441C>T	p.Cys147Cys	synonymous	Exon 2 of 2	ENSP00000525661.1
	TMEM187	ENST00000855603.1		c.441C>T	p.Cys147Cys	synonymous	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 23729 AN: 112782 Hom.: 2525 Cov.: 25

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0685

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.319 AC: 54025 AN: 169383 AF XY: 0.310

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.719

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.303

GnomAD4 exome AF: 0.219 AC: 238542 AN: 1089622 Hom.: 24096 Cov.: 33 AF XY: 0.230 AC XY: 82565 AN XY: 358806

African (AFR) AF: 0.108 AC: 2852 AN: 26375

American (AMR) AF: 0.572 AC: 19774 AN: 34594

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 5555 AN: 19343

East Asian (EAS) AF: 0.723 AC: 21729 AN: 30064

South Asian (SAS) AF: 0.559 AC: 30056 AN: 53729

European-Finnish (FIN) AF: 0.170 AC: 5930 AN: 34912

Middle Eastern (MID) AF: 0.379 AC: 1523 AN: 4017

European-Non Finnish (NFE) AF: 0.165 AC: 139125 AN: 840676

Other (OTH) AF: 0.261 AC: 11998 AN: 45912

GnomAD4 genome AF: 0.210 AC: 23735 AN: 112835 Hom.: 2530 Cov.: 25 AF XY: 0.221 AC XY: 7735 AN XY: 35035

African (AFR) AF: 0.113 AC: 3530 AN: 31236

American (AMR) AF: 0.422 AC: 4524 AN: 10728

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 694 AN: 2658

East Asian (EAS) AF: 0.724 AC: 2553 AN: 3526

South Asian (SAS) AF: 0.576 AC: 1591 AN: 2762

European-Finnish (FIN) AF: 0.170 AC: 1063 AN: 6260

Middle Eastern (MID) AF: 0.319 AC: 69 AN: 216

European-Non Finnish (NFE) AF: 0.174 AC: 9252 AN: 53217

Other (OTH) AF: 0.266 AC: 412 AN: 1546

Alfa AF: 0.213 Hom.: 12544

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs6571303; hg19: chrX-153247954; COSMIC: COSV64141106; COSMIC: COSV64141106;