19-42315054-G-A

Variant summary

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

The NM_173633.3(TMEM145):​c.482G>A​(p.Arg161Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TMEM145
NM_173633.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86
Variant links:
Genes affected
TMEM145 (HGNC:26912): (transmembrane protein 145) Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. 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 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=0.19087127).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM145NM_173633.3 linkuse as main transcriptc.482G>A p.Arg161Gln missense_variant 6/15 ENST00000301204.8 NP_775904.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM145ENST00000301204.8 linkuse as main transcriptc.482G>A p.Arg161Gln missense_variant 6/152 NM_173633.3 ENSP00000301204
TMEM145ENST00000673205.1 linkuse as main transcriptc.482G>A p.Arg161Gln missense_variant 6/14 ENSP00000499841
TMEM145ENST00000673187.1 linkuse as main transcriptc.524G>A p.Arg175Gln missense_variant 6/15 ENSP00000500040 P1
TMEM145ENST00000598766.1 linkuse as main transcriptc.554G>A p.Arg185Gln missense_variant 6/145 ENSP00000470827

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152160
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251474
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135910
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:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461884
Hom.:
0
Cov.:
35
AF XY:
0.0000303
AC XY:
22
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74332
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:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000109
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsDec 27, 2022The c.482G>A (p.R161Q) alteration is located in exon 6 (coding exon 6) of the TMEM145 gene. This alteration results from a G to A substitution at nucleotide position 482, causing the arginine (R) at amino acid position 161 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
0.073
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.013
T;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.67
N;.
MutationTaster
Benign
0.96
D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.010
N;.
REVEL
Benign
0.042
Sift
Benign
0.46
T;.
Sift4G
Benign
0.49
T;T
Polyphen
0.022
B;.
Vest4
0.18
MutPred
0.58
Gain of ubiquitination at K156 (P = 0.0762);.;
MVP
0.28
MPC
0.56
ClinPred
0.22
T
GERP RS
4.6
Varity_R
0.098
gMVP
0.27

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: rs769767615; hg19: chr19-42819206; API