Genetic Variant NM_003492.3:c.307C>T (chrX-153982369-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_003492.3(TMEM187):c.307C>T(p.Arg103Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,201,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 0 hem., cov: 26)

Exomes 𝑓: 0.0000092 ( 0 hom. 4 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

BS2

High Hemizygotes in GnomAdExome4 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.307C>T	p.Arg103Cys	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.307C>T	p.Arg103Cys	missense	Exon 2 of 2	ENSP00000358999.4	Q14656
TMEM187	ENST00000855602.1		c.307C>T	p.Arg103Cys	missense	Exon 2 of 2	ENSP00000525661.1
TMEM187	ENST00000855603.1		c.307C>T	p.Arg103Cys	missense	Exon 3 of 3	ENSP00000525662.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

113671

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

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:

0.000648

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

160433

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000773

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:

0.00

GnomAD4 exome

AF:

0.00000919

AC:

AN:

1087642

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

356460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26316

American (AMR)

AF:

0.0000582

AC:

AN:

34348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19252

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29887

South Asian (SAS)

AF:

0.00

AC:

AN:

53354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4035

European-Non Finnish (NFE)

AF:

0.00000834

AC:

AN:

839349

Other (OTH)

AF:

0.00

AC:

AN:

45781

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000264

AC:

AN:

113671

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35813

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31392

American (AMR)

AF:

0.000184

AC:

AN:

10863

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3621

South Asian (SAS)

AF:

0.00

AC:

AN:

2852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6369

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53445

Other (OTH)

AF:

0.000648

AC:

AN:

1544

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

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:

0.000521

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.29

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.86

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.4

PhyloP100

1.9

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.77

MutPred

0.37

Loss of MoRF binding (P = 0.0032)

MVP

0.23

MPC

0.78

ClinPred

0.97

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.89

Mutation Taster

=89/11

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