X-153974136-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.-214+1276G>T		intron_variant		ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.-214+1276G>T		intron_variant		1	NM_003492.3	P1
TMEM187	ENST00000425274.1	c.-214+1250G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.382 AC: 42328 AN: 110802 Hom.: 7978 Cov.: 24 AF XY: 0.383 AC XY: 12635 AN XY: 33032

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

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.412

Alfa AF: 0.193 Hom.: 1491

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.49
Dann	Benign	0.39

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: rs2266887; hg19: chrX-153239587;