chr11-129852583-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138788.5(TMEM45B):​c.101G>A​(p.Arg34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMEM45B
NM_138788.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0590
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034696817).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM45BNM_138788.5 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 2/6 ENST00000281441.8 NP_620143.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM45BENST00000281441.8 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 2/62 NM_138788.5 ENSP00000281441 P1
TMEM45BENST00000524567.1 linkuse as main transcriptc.101G>A p.Arg34Gln missense_variant 2/61 ENSP00000436293 P1
TMEM45BENST00000527754.1 linkuse as main transcriptn.252G>A non_coding_transcript_exon_variant 3/65
TMEM45BENST00000529381.1 linkuse as main transcriptn.137G>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152098
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251476
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000205
AC:
3
AN:
1461722
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsOct 10, 2023The c.101G>A (p.R34Q) alteration is located in exon 2 (coding exon 1) of the TMEM45B gene. This alteration results from a G to A substitution at nucleotide position 101, causing the arginine (R) at amino acid position 34 to be replaced by a glutamine (Q). 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
0.076
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.7
DANN
Benign
0.83
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.39
.;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.17
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.55
N;N
REVEL
Benign
0.0070
Sift
Benign
0.52
T;T
Sift4G
Benign
0.52
T;T
Polyphen
0.0
B;B
Vest4
0.15
MVP
0.16
MPC
0.12
ClinPred
0.029
T
GERP RS
-0.99
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.022
gMVP
0.32

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.

Other links and lift over

dbSNP: rs369904524; hg19: chr11-129722478; COSMIC: COSV55653234; API