X-153982159-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003492.3(TMEM187):c.97G>C(p.Val33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,211,711 control chromosomes in the GnomAD database, including 1 homozygotes. There are 673 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V33M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., 51 hem., cov: 25)
  • Exomes 𝑓: 0.0018 (0 hom. 622 hem.)
• Consequence: TMEM187 NM_003492.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.318

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0135162175).
• BP6: Variant X-153982159-G-C is Benign according to our data. Variant chrX-153982159-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 711110.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153982159-G-C is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3	c.97G>C	p.Val33Leu	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5	c.97G>C	p.Val33Leu	missense_variant	2/2	1	NM_003492.3	P1
TMEM187	ENST00000425274.1	c.97G>C	p.Val33Leu	missense_variant	2/2	5
TMEM187	ENST00000431598.1	c.97G>C	p.Val33Leu	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 135 AN: 113523 Hom.: 1 Cov.: 25 AF XY: 0.00143 AC XY: 51 AN XY: 35657

Gnomad AFR AF: 0.000319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000462

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00299

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.00130

GnomAD3 exomes AF: 0.00102 AC: 185 AN: 181782 Hom.: 0 AF XY: 0.00114 AC XY: 76 AN XY: 66796

Gnomad AFR exome AF: 0.000305

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00244

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.000668

GnomAD4 exome AF: 0.00180 AC: 1973 AN: 1098135 Hom.: 0 Cov.: 31 AF XY: 0.00171 AC XY: 622 AN XY: 363545

Gnomad4 AFR exome AF: 0.000265

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00220

Gnomad4 NFE exome AF: 0.00215

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00119 AC: 135 AN: 113576 Hom.: 1 Cov.: 25 AF XY: 0.00143 AC XY: 51 AN XY: 35720

Gnomad4 AFR AF: 0.000318

Gnomad4 AMR AF: 0.000461

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00299

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.00129

Alfa AF: 0.00126 Hom.: 21

Bravo AF: 0.000960

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00173 AC: 5

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00119 AC: 8

ExAC AF: 0.00121 AC: 147

EpiCase AF: 0.00147

EpiControl AF: 0.00148

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

Apr 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	8.6
Dann	Benign	0.90
DEOGEN2	Benign	0.041	T;.;.
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0083	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N;N;D
REVEL	Benign	0.10
Sift	Benign	0.041	D;D;.
Sift4G	Benign	0.075	T;D;D
Polyphen		0.58	P;.;.
Vest4		0.35
MutPred		0.24		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.12
MPC		0.30
ClinPred		0.0077	T
GERP RS		-0.96
Varity_R		0.12
gMVP		0.24

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: rs139864308; hg19: chrX-153247610;