X-153982227-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003492.3(TMEM187):c.165G>A(p.Pro55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,211,641 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 62 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 7 hem., cov: 25)
  • Exomes 𝑓: 0.00016 (0 hom. 55 hem.)
• Consequence: TMEM187 NM_003492.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-153982227-G-A is Benign according to our data. Variant chrX-153982227-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 707842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.165G>A	p.Pro55=	synonymous_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.165G>A	p.Pro55=	synonymous_variant	2/2	1	NM_003492.3	P1
TMEM187	ENST00000425274.1	c.165G>A	p.Pro55=	synonymous_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.000141 AC: 16 AN: 113630 Hom.: 0 Cov.: 25 AF XY: 0.000196 AC XY: 7 AN XY: 35758

Gnomad AFR AF: 0.000415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000924

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000374

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000937 AC: 17 AN: 181366 Hom.: 0 AF XY: 0.000150 AC XY: 10 AN XY: 66594

Gnomad AFR exome AF: 0.000305

Gnomad AMR exome AF: 0.000256

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000749

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000158 AC: 173 AN: 1097957 Hom.: 0 Cov.: 31 AF XY: 0.000151 AC XY: 55 AN XY: 363467

Gnomad4 AFR exome AF: 0.000644

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.000141 AC: 16 AN: 113684 Hom.: 0 Cov.: 25 AF XY: 0.000195 AC XY: 7 AN XY: 35822

Gnomad4 AFR AF: 0.000414

Gnomad4 AMR AF: 0.0000923

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000374

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000218 Hom.: 3

Bravo AF: 0.000193

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	4.9
Dann	Benign	0.86

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: rs139416361; hg19: chrX-153247678; COSMIC: COSV64141710; COSMIC: COSV64141710;