Variant 11-129854775-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138788.5(TMEM45B):c.344G>A(p.Gly115Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TMEM45B
NM_138788.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

TMEM45B (HGNC:25194): (transmembrane protein 45B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM45B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM45B	NM_138788.5 linkuse as main transcript	c.344G>A	p.Gly115Glu	missense_variant	3/6	ENST00000281441.8	NP_620143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM45B	ENST00000281441.8 linkuse as main transcript	c.344G>A	p.Gly115Glu	missense_variant	3/6	2	NM_138788.5	ENSP00000281441	P1
TMEM45B	ENST00000524567.1 linkuse as main transcript	c.344G>A	p.Gly115Glu	missense_variant	3/6	1		ENSP00000436293	P1
TMEM45B	ENST00000527754.1 linkuse as main transcript	n.495G>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152248

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:

0.000769

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:

0.0000517

AC:

AN:

251408

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

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:

0.00000479

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

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:

0.0000263

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000576

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

Nov 02, 2023

The c.344G>A (p.G115E) alteration is located in exon 3 (coding exon 2) of the TMEM45B gene. This alteration results from a G to A substitution at nucleotide position 344, causing the glycine (G) at amino acid position 115 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

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.094

T;T

Polyphen

0.42

B;B

Vest4

0.89

MutPred

0.68

Loss of catalytic residue at V116 (P = 0.0473);Loss of catalytic residue at V116 (P = 0.0473);

MVP

0.57

MPC

0.59

ClinPred

0.91

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.84

gMVP

0.88

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

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