X-153982475-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003492.3(TMEM187):c.413G>A(p.Arg138Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,202,302 control chromosomes in the GnomAD database, including 64 homozygotes. There are 908 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.014 (37 hom., 449 hem., cov: 26)
  • Exomes 𝑓: 0.0016 (27 hom. 459 hem.)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015996099).
• BP6: Variant X-153982475-G-A is Benign according to our data. Variant chrX-153982475-G-A is described in ClinVar as [Benign]. Clinvar id is 711792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (1631/113489) while in subpopulation AFR AF= 0.0493 (1546/31361). AF 95% confidence interval is 0.0473. There are 37 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.413G>A	p.Arg138Gln	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.413G>A	p.Arg138Gln	missense_variant	2/2	1	NM_003492.3	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 1630 AN: 113435 Hom.: 37 Cov.: 26 AF XY: 0.0127 AC XY: 451 AN XY: 35571

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00555

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00784

GnomAD3 exomes AF: 0.00490 AC: 819 AN: 167271 Hom.: 13 AF XY: 0.00340 AC XY: 193 AN XY: 56691

Gnomad AFR exome AF: 0.0569

Gnomad AMR exome AF: 0.00323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000276

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.00158 AC: 1717 AN: 1088813 Hom.: 27 Cov.: 33 AF XY: 0.00128 AC XY: 459 AN XY: 358221

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000667

Gnomad4 SAS exome AF: 0.000131

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000191

Gnomad4 OTH exome AF: 0.00349

GnomAD4 genome AF: 0.0144 AC: 1631 AN: 113489 Hom.: 37 Cov.: 26 AF XY: 0.0126 AC XY: 449 AN XY: 35635

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.00554

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000225

Gnomad4 OTH AF: 0.00774

Alfa AF: 0.00352 Hom.: 44

Bravo AF: 0.0170

ESP6500AA AF: 0.0519 AC: 199

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00493 AC: 598

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.91	T
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.17
Dann	Benign	0.86
DEOGEN2	Benign	0.0014	T
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.0030
Sift	Benign	0.33	T
Sift4G	Benign	0.47	T
Polyphen		0.010	B
Vest4		0.023
MVP		0.12
MPC		0.18
ClinPred		0.0030	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.30

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: rs36085378; hg19: chrX-153247926;