X-153982503-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM187	NM_003492.3	c.441C>T	p.Cys147Cys	synonymous_variant	Exon 2 of 2	ENST00000369982.5	NP_003483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM187	ENST00000369982.5	c.441C>T	p.Cys147Cys	synonymous_variant	Exon 2 of 2	1	NM_003492.3	ENSP00000358999.4
TMEM187	ENST00000425274.1	c.*243C>T		downstream_gene_variant		5		ENSP00000390108.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 23729 AN: 112782 Hom.: 2525 Cov.: 25 AF XY: 0.221 AC XY: 7731 AN XY: 34972

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

GnomAD3 exomes AF: 0.319 AC: 54025 AN: 169383 Hom.: 8654 AF XY: 0.310 AC XY: 17945 AN XY: 57925

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 SAS exome AF: 0.558

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

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.261

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.266

Alfa AF: 0.215 Hom.: 9535

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

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