Variant 11-129857436-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138788.5(TMEM45B):c.694G>A(p.Val232Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

TMEM45B
NM_138788.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.243

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018789023).

BP6

Variant 11-129857436-G-A is Benign according to our data. Variant chr11-129857436-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2401163.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM45B	NM_138788.5 linkuse as main transcript	c.694G>A	p.Val232Ile	missense_variant	5/6	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.694G>A	p.Val232Ile	missense_variant	5/6	2	NM_138788.5	ENSP00000281441	P1
TMEM45B	ENST00000524567.1 linkuse as main transcript	c.694G>A	p.Val232Ile	missense_variant	5/6	1		ENSP00000436293	P1
TMEM45B	ENST00000527754.1 linkuse as main transcript	n.845G>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251392

Hom.:

AF XY:

0.000250

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000215

AC:

315

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

145

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000190

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.56

DANN

Benign

0.30

DEOGEN2

Benign

0.0046

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.097

.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.030

Sift

Benign

0.64

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.013

B;B

Vest4

0.099

MVP

0.11

MPC

0.086

ClinPred

0.0018

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.11

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