19-42314317-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173633.3(TMEM145):​c.166C>G​(p.Arg56Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TMEM145
NM_173633.3 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM145NM_173633.3 linkc.166C>G p.Arg56Gly missense_variant Exon 2 of 15 ENST00000301204.8 NP_775904.2 Q8NBT3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM145ENST00000301204.8 linkc.166C>G p.Arg56Gly missense_variant Exon 2 of 15 2 NM_173633.3 ENSP00000301204.2 Q8NBT3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251474
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135916
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461878
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727244
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.166C>G (p.R56G) alteration is located in exon 2 (coding exon 2) of the TMEM145 gene. This alteration results from a C to G substitution at nucleotide position 166, causing the arginine (R) at amino acid position 56 to be replaced by a glycine (G). 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
0.68
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.0
D;.
REVEL
Benign
0.26
Sift
Uncertain
0.020
D;.
Sift4G
Uncertain
0.019
D;D
Polyphen
1.0
D;.
Vest4
0.85
MutPred
0.51
Loss of methylation at R56 (P = 0.0336);Loss of methylation at R56 (P = 0.0336);
MVP
0.56
MPC
1.0
ClinPred
0.96
D
GERP RS
4.5
Varity_R
0.50
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs746766012; hg19: chr19-42818469; API