chrX-153982271-C-T

Variant names:

• chrX-153982271-C-T
• rs2266890
• NM_003492.3:c.209C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict 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 (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
• Publications: 23 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 -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.

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.209C>T	p.Ser70Leu	missense	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.209C>T	p.Ser70Leu	missense	Exon 2 of 2	ENSP00000358999.4	Q14656
	TMEM187	ENST00000855602.1		c.209C>T	p.Ser70Leu	missense	Exon 2 of 2	ENSP00000525661.1
	TMEM187	ENST00000855603.1		c.209C>T	p.Ser70Leu	missense	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23941 AN: 113172 Hom.: 2508 Cov.: 25

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

GnomAD2 exomes AF: 0.323 AC: 58026 AN: 179707 AF XY: 0.321

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 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

African (AFR) AF: 0.107 AC: 2830 AN: 26394

American (AMR) AF: 0.573 AC: 20132 AN: 35111

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 5563 AN: 19355

East Asian (EAS) AF: 0.721 AC: 21757 AN: 30181

South Asian (SAS) AF: 0.560 AC: 30277 AN: 54111

European-Finnish (FIN) AF: 0.175 AC: 7024 AN: 40054

Middle Eastern (MID) AF: 0.381 AC: 1556 AN: 4089

European-Non Finnish (NFE) AF: 0.166 AC: 139675 AN: 841852

Other (OTH) AF: 0.261 AC: 12027 AN: 46054

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

African (AFR) AF: 0.111 AC: 3493 AN: 31341

American (AMR) AF: 0.423 AC: 4574 AN: 10803

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 694 AN: 2660

East Asian (EAS) AF: 0.724 AC: 2584 AN: 3568

South Asian (SAS) AF: 0.586 AC: 1657 AN: 2829

European-Finnish (FIN) AF: 0.175 AC: 1100 AN: 6296

Middle Eastern (MID) AF: 0.327 AC: 71 AN: 217

European-Non Finnish (NFE) AF: 0.175 AC: 9315 AN: 53274

Other (OTH) AF: 0.267 AC: 414 AN: 1553

Alfa AF: 0.200 Hom.: 14636

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 v4.9

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
PhyloP100		1.8
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
Mutation Taster		=99/1	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: rs2266890; hg19: chrX-153247722; COSMIC: COSV64141847; COSMIC: COSV64141847;