Genetic Variant TMEM25:c.*540G>A (chr11-118535120-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032780.4(TMEM25):c.*540G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,016,926 control chromosomes in the GnomAD database, including 11,554 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 0.16 ( 2453 hom., cov: 32)

Exomes 𝑓: 0.14 ( 9101 hom. )

Consequence

TMEM25
NM_032780.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.494

Publications

17 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM25	NM_032780.4 link	c.*540G>A		3_prime_UTR_variant	Exon 9 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.*540G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_032780.4	ENSP00000315635.5		Q86YD3-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24505

AN:

151918

Hom.:

2456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0962

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.138

AC:

119110

AN:

864890

Hom.:

9101

Cov.:

AF XY:

0.138

AC XY:

55471

AN XY:

400698

show subpopulations

African (AFR)

AF:

0.173

AC:

2911

AN:

16782

American (AMR)

AF:

0.0757

AC:

237

AN:

3130

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

856

AN:

6126

East Asian (EAS)

AF:

0.484

AC:

2498

AN:

5166

South Asian (SAS)

AF:

0.328

AC:

5917

AN:

18014

European-Finnish (FIN)

AF:

0.148

AC:

306

AN:

2062

Middle Eastern (MID)

AF:

0.160

AC:

276

AN:

1720

European-Non Finnish (NFE)

AF:

0.129

AC:

101123

AN:

782714

Other (OTH)

AF:

0.171

AC:

4986

AN:

29176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7092

14184

21276

28368

35460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5114

10228

15342

20456

25570

<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:

0.161

AC:

24518

AN:

152036

Hom.:

2453

Cov.:

AF XY:

0.166

AC XY:

12308

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.174

AC:

7224

AN:

41450

American (AMR)

AF:

0.0960

AC:

1467

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3468

East Asian (EAS)

AF:

0.493

AC:

2532

AN:

5140

South Asian (SAS)

AF:

0.338

AC:

1629

AN:

4824

European-Finnish (FIN)

AF:

0.163

AC:

1727

AN:

10574

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8923

AN:

67988

Other (OTH)

AF:

0.157

AC:

332

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1033

2065

3098

4130

5163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.133

Hom.:

1570

Bravo

AF:

0.155

Asia WGS

AF:

0.424

AC:

1472

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.49

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