chr11-129858651-A-G

Variant summary

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

The NM_138788.5(TMEM45B):ā€‹c.794A>Gā€‹(p.Gln265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,572,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 33)
Exomes š‘“: 0.00020 ( 0 hom. )

Consequence

TMEM45B
NM_138788.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
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=0.038439542).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM45BNM_138788.5 linkuse as main transcriptc.794A>G p.Gln265Arg missense_variant 6/6 ENST00000281441.8 NP_620143.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM45BENST00000281441.8 linkuse as main transcriptc.794A>G p.Gln265Arg missense_variant 6/62 NM_138788.5 ENSP00000281441 P1
TMEM45BENST00000524567.1 linkuse as main transcriptc.794A>G p.Gln265Arg missense_variant 6/61 ENSP00000436293 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152202
Hom.:
0
Cov.:
33
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:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000102
AC:
19
AN:
185936
Hom.:
0
AF XY:
0.0000919
AC XY:
9
AN XY:
97920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000582
Gnomad NFE exome
AF:
0.000232
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000196
AC:
278
AN:
1420748
Hom.:
0
Cov.:
30
AF XY:
0.000191
AC XY:
134
AN XY:
702184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000522
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000790
Gnomad4 NFE exome
AF:
0.000242
Gnomad4 OTH exome
AF:
0.000136
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74374
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:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000123
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000923
AC:
11

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 GeneticsJan 10, 2023The c.794A>G (p.Q265R) alteration is located in exon 6 (coding exon 5) of the TMEM45B gene. This alteration results from a A to G substitution at nucleotide position 794, causing the glutamine (Q) at amino acid position 265 to be replaced by an arginine (R). 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
0.069
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.50
.;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
0.99
D;D
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.031
Sift
Benign
0.091
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.0040
B;B
Vest4
0.032
MVP
0.32
MPC
0.12
ClinPred
0.079
T
GERP RS
4.6
Varity_R
0.19
gMVP
0.35

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: rs143243670; hg19: chr11-129728546; API