X-153974136-G-T

Variant names:

• chrX-153974136-G-T
• rs2266887
• NM_003492.3:c.-214+1276G>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.-214+1276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 110,857 control chromosomes in the GnomAD database, including 7,987 homozygotes. There are 12,685 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 0.38 (7987 hom., 12685 hem., cov: 24)
• Consequence: TMEM187 NM_003492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 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+1276G>T		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+1276G>T		intron	N/A	ENSP00000358999.4
	TMEM187	ENST00000425274.1	TSL:5	c.-214+1250G>T		intron	N/A	ENSP00000390108.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 42328 AN: 110802 Hom.: 7978 Cov.: 24

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.0689

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.382 AC: 42391 AN: 110857 Hom.: 7987 Cov.: 24 AF XY: 0.383 AC XY: 12685 AN XY: 33097

African (AFR) AF: 0.695 AC: 20931 AN: 30131

American (AMR) AF: 0.498 AC: 5243 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 675 AN: 2639

East Asian (EAS) AF: 0.755 AC: 2654 AN: 3517

South Asian (SAS) AF: 0.593 AC: 1569 AN: 2647

European-Finnish (FIN) AF: 0.171 AC: 1031 AN: 6028

Middle Eastern (MID) AF: 0.356 AC: 77 AN: 216

European-Non Finnish (NFE) AF: 0.180 AC: 9536 AN: 52951

Other (OTH) AF: 0.412 AC: 628 AN: 1526

Alfa AF: 0.193 Hom.: 1491

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-2.4
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: rs2266887; hg19: chrX-153239587;