rs2266888

Variant names:

• chrX-153974269-G-A
• rs2266888
• NM_003492.3:c.-214+1409G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153974269-G-A
• chrX-153974269-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003492.3(TMEM187):​c.-214+1409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 111,074 control chromosomes in the GnomAD database, including 2,793 homozygotes. There are 7,873 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 0.23 (2793 hom., 7873 hem., cov: 23)
• Consequence: TMEM187 NM_003492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 7 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 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.-214+1409G>A		intron	N/A	NP_003483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.-214+1409G>A		intron	N/A	ENSP00000358999.4
	TMEM187	ENST00000425274.1	TSL:5	c.-214+1383G>A		intron	N/A	ENSP00000390108.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 25222 AN: 111017 Hom.: 2785 Cov.: 23

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 25243 AN: 111074 Hom.: 2793 Cov.: 23 AF XY: 0.236 AC XY: 7873 AN XY: 33322

African (AFR) AF: 0.168 AC: 5125 AN: 30570

American (AMR) AF: 0.428 AC: 4486 AN: 10475

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 669 AN: 2640

East Asian (EAS) AF: 0.753 AC: 2637 AN: 3501

South Asian (SAS) AF: 0.589 AC: 1534 AN: 2605

European-Finnish (FIN) AF: 0.167 AC: 999 AN: 5967

Middle Eastern (MID) AF: 0.316 AC: 68 AN: 215

European-Non Finnish (NFE) AF: 0.175 AC: 9265 AN: 52915

Other (OTH) AF: 0.272 AC: 412 AN: 1513

Alfa AF: 0.223 Hom.: 7050

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.78
PhyloP100		-0.61
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: rs2266888; hg19: chrX-153239720;