Variant 11-118533068-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032780.4(TMEM25):c.534C>A(p.Asp178Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TMEM25
NM_032780.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14825404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM25	NM_032780.4 link	c.534C>A	p.Asp178Glu	missense_variant	4/9	ENST00000313236.10	NP_116169.2	Q86YD3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM25	ENST00000313236.10 link	c.534C>A	p.Asp178Glu	missense_variant	4/9	1	NM_032780.4	ENSP00000315635.5		Q86YD3-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

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

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251322

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS 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:

0.00000889

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.534C>A (p.D178E) alteration is located in exon 4 (coding exon 3) of the TMEM25 gene. This alteration results from a C to A substitution at nucleotide position 534, causing the aspartic acid (D) at amino acid position 178 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

.;.;.;.;.;.;T;T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.78

.;T;T;T;T;T;T;T;.

M_CAP

Benign

0.0046

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;L;L;L;.;.;.;L;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.16

T;T;T;D;D;T;D;D;T

Sift4G

Benign

0.090

T;T;T;T;D;T;T;T;T

Polyphen

0.0060

B;B;.;D;.;B;D;P;B

Vest4

0.17

MutPred

0.75

Loss of stability (P = 0.2353);Loss of stability (P = 0.2353);Loss of stability (P = 0.2353);Loss of stability (P = 0.2353);.;.;Loss of stability (P = 0.2353);Loss of stability (P = 0.2353);Loss of stability (P = 0.2353);

MVP

0.12

MPC

0.14

ClinPred

0.16

GERP RS

5.1

Varity_R

0.16

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over