rs2266888

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.-214+1409G>A		intron_variant		ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.-214+1409G>A		intron_variant		1	NM_003492.3	P1
TMEM187	ENST00000425274.1	c.-214+1383G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 25222 AN: 111017 Hom.: 2785 Cov.: 23 AF XY: 0.236 AC XY: 7854 AN XY: 33255

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

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.272

Alfa AF: 0.219 Hom.: 4575

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.78

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: rs2266888; hg19: chrX-153239720;