Genetic Variant TMEM187:p.Trp5Ser (chrX-153982076-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003492.3(TMEM187):c.14G>C(p.Trp5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,211,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.686

Publications

0 publications found

Variant links:

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]

TMEM187 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017345697).

BP6

Variant X-153982076-G-C is Benign according to our data. Variant chrX-153982076-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2255178.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 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.14G>C	p.Trp5Ser	missense	Exon 2 of 2	NP_003483.1	Q14656

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM187	ENST00000369982.5	TSL:1 MANE Select	c.14G>C	p.Trp5Ser	missense	Exon 2 of 2	ENSP00000358999.4	Q14656
TMEM187	ENST00000855602.1		c.14G>C	p.Trp5Ser	missense	Exon 2 of 2	ENSP00000525661.1
TMEM187	ENST00000855603.1		c.14G>C	p.Trp5Ser	missense	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

113711

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000478

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000770

AC:

AN:

181915

AF XY:

0.0000599

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.0000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1098080

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363500

show subpopulations

African (AFR)

AF:

0.000417

AC:

AN:

26403

American (AMR)

AF:

0.0000568

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54143

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842139

Other (OTH)

AF:

0.0000868

AC:

AN:

46089

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000132

AC:

AN:

113711

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

35843

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

31384

American (AMR)

AF:

0.00

AC:

AN:

10855

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2665

East Asian (EAS)

AF:

0.00

AC:

AN:

3611

South Asian (SAS)

AF:

0.00

AC:

AN:

2878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53459

Other (OTH)

AF:

0.00

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.43

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.00084

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.26

M_CAP

Benign

0.0012

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

PhyloP100

-0.69

PrimateAI

Benign

0.36

PROVEAN

Benign

0.57

REVEL

Benign

0.036

Sift

Benign

0.90

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.072

MVP

0.092

MPC

0.26

ClinPred

0.012

GERP RS

-2.3

Varity_R

0.074

gMVP

0.37

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over