chrX-153982271-C-T

Position:

• chrX-153982271-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003492.3(TMEM187):​c.209C>T​(p.Ser70Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,210,430 control chromosomes in the GnomAD database, including 26,738 homozygotes. There are 91,910 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (2513 hom., 7981 hem., cov: 25)
  • Exomes 𝑓: 0.22 (24225 hom. 83929 hem.)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3416005E-6).
• 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/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3	c.209C>T	p.Ser70Leu	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.209C>T	p.Ser70Leu	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4
TMEM187	ENST00000425274.1	c.*11C>T		downstream_gene_variant		5		ENSP00000390108.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23941 AN: 113172 Hom.: 2508 Cov.: 25 AF XY: 0.226 AC XY: 7974 AN XY: 35326

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0698

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.319

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.257

GnomAD3 exomes AF: 0.323 AC: 58026 AN: 179707 Hom.: 8868 AF XY: 0.321 AC XY: 20978 AN XY: 65329

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.722

Gnomad SAS exome AF: 0.564

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.303

GnomAD4 exome AF: 0.220 AC: 240841 AN: 1097201 Hom.: 24225 Cov.: 33 AF XY: 0.231 AC XY: 83929 AN XY: 362873

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.721

Gnomad4 SAS exome AF: 0.560

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.212 AC: 23950 AN: 113229 Hom.: 2513 Cov.: 25 AF XY: 0.225 AC XY: 7981 AN XY: 35393

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.267

Alfa AF: 0.206 Hom.: 13784

Bravo AF: 0.229

TwinsUK AF: 0.170 AC: 631

ALSPAC AF: 0.170 AC: 490

ESP6500AA AF: 0.107 AC: 412

ESP6500EA AF: 0.179 AC: 1205

ExAC AF: 0.305 AC: 37067

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.97	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.8
DANN	Benign	0.83
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.064
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.044
MPC		0.14
ClinPred		0.0056	T
GERP RS		0.24
Varity_R		0.050
gMVP		0.55

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: rs2266890; hg19: chrX-153247722; COSMIC: COSV64141847; COSMIC: COSV64141847;