X-153982282-A-G

Variant names:

• chrX-153982282-A-G
• rs781817194
• NM_003492.3:c.220A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003492.3(TMEM187):​c.220A>G​(p.Arg74Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,210,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000061 (0 hom. 20 hem.)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06907681).
• BS2: High Hemizygotes in GnomAdExome4 at 20 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	NM_003492.3	MANE Select	c.220A>G	p.Arg74Gly	missense	Exon 2 of 2	NP_003483.1	Q14656

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.220A>G	p.Arg74Gly	missense	Exon 2 of 2	ENSP00000358999.4	Q14656
	TMEM187	ENST00000855602.1		c.220A>G	p.Arg74Gly	missense	Exon 2 of 2	ENSP00000525661.1
	TMEM187	ENST00000855603.1		c.220A>G	p.Arg74Gly	missense	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes AF: 0.0000176 AC: 2 AN: 113432 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000223 AC: 4 AN: 179510 AF XY: 0.0000306

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000253

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000611 AC: 67 AN: 1097217 Hom.: 0 Cov.: 33 AF XY: 0.0000551 AC XY: 20 AN XY: 362993

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.0000284 AC: 1 AN: 35171

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30193

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39909

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.0000760 AC: 64 AN: 841971

Other (OTH) AF: 0.0000217 AC: 1 AN: 46053

GnomAD4 genome AF: 0.0000176 AC: 2 AN: 113432 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35612

African (AFR) AF: 0.00 AC: 0 AN: 31299

American (AMR) AF: 0.00 AC: 0 AN: 10810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.00 AC: 0 AN: 2854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000375 AC: 2 AN: 53373

Other (OTH) AF: 0.00 AC: 0 AN: 1537

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.038
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Polyphen		0.10	B
Vest4		0.11
MutPred		0.33		Loss of helix (P = 0.0104)
MVP		0.095
MPC		0.28
ClinPred		0.036	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.56
Mutation Taster		=95/5	polymorphism

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: rs781817194; hg19: chrX-153247733;