dbSNP rs6589664: TMEM25:p.Pro299Pro (chr11-118534089-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_032780.4(TMEM25):c.897G>A(p.Pro299Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,613,730 control chromosomes in the GnomAD database, including 69,962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6150 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63812 hom. )

Consequence

TMEM25
NM_032780.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.70

Publications

28 publications found

Variant links:

Genes affected

TMEM25 (HGNC:25890): (transmembrane protein 25) Predicted to be involved in negative regulation of excitatory postsynaptic potential and regulation of protein stability. Predicted to be located in late endosome and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.041).

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM25	NM_032780.4 link	c.897G>A	p.Pro299Pro	synonymous_variant	Exon 7 of 9	ENST00000313236.10	NP_116169.2	Q86YD3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM25	ENST00000313236.10 link	c.897G>A	p.Pro299Pro	synonymous_variant	Exon 7 of 9	1	NM_032780.4	ENSP00000315635.5		Q86YD3-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41282

AN:

151814

Hom.:

6131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.376

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.302

AC:

75803

AN:

251396

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.549

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.288

AC:

420787

AN:

1461796

Hom.:

63812

Cov.:

AF XY:

0.283

AC XY:

205823

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.181

AC:

6045

AN:

33480

American (AMR)

AF:

0.537

AC:

24018

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

7734

AN:

26136

East Asian (EAS)

AF:

0.312

AC:

12388

AN:

39700

South Asian (SAS)

AF:

0.152

AC:

13098

AN:

86256

European-Finnish (FIN)

AF:

0.312

AC:

16689

AN:

53408

Middle Eastern (MID)

AF:

0.286

AC:

1651

AN:

5768

European-Non Finnish (NFE)

AF:

0.290

AC:

322529

AN:

1111936

Other (OTH)

AF:

0.275

AC:

16635

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18235

36470

54705

72940

91175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10624

21248

31872

42496

53120

<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:

0.272

AC:

41334

AN:

151934

Hom.:

6150

Cov.:

AF XY:

0.272

AC XY:

20229

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.189

AC:

7842

AN:

41454

American (AMR)

AF:

0.411

AC:

6271

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1069

AN:

3470

East Asian (EAS)

AF:

0.267

AC:

1379

AN:

5160

South Asian (SAS)

AF:

0.141

AC:

678

AN:

4810

European-Finnish (FIN)

AF:

0.308

AC:

3247

AN:

10550

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19810

AN:

67906

Other (OTH)

AF:

0.291

AC:

614

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1481

2962

4442

5923

7404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.292

Hom.:

9398

Bravo

AF:

0.282

Asia WGS

AF:

0.194

AC:

675

AN:

3478

EpiCase

AF:

0.289

EpiControl

AF:

0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.68

(source)

DANN

Benign

0.85

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over