19-12737608-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004317.4(GET3):​c.103C>T​(p.Arg35Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GET3
NM_004317.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05
Variant links:
Genes affected
GET3 (HGNC:752): (guided entry of tail-anchored proteins factor 3, ATPase) This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30848262).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GET3NM_004317.4 linkc.103C>T p.Arg35Cys missense_variant Exon 1 of 7 ENST00000357332.8 NP_004308.2 O43681
GET3NM_001371488.1 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 8 NP_001358417.1
GET3NM_001371489.1 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 8 NP_001358418.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GET3ENST00000357332.8 linkc.103C>T p.Arg35Cys missense_variant Exon 1 of 7 1 NM_004317.4 ENSP00000349887.3 O43681
GET3ENST00000591090.5 linkc.103C>T p.Arg35Cys missense_variant Exon 2 of 8 5 ENSP00000466379.1 O43681
GET3ENST00000590633.1 linkn.112C>T non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459282
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725978
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.103C>T (p.R35C) alteration is located in exon 1 (coding exon 1) of the ASNA1 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the arginine (R) at amino acid position 35 to be replaced by a cysteine (C). 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
0.25
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.81
D;.;D;.
Eigen
Benign
-0.082
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
.;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;L;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.7
.;.;D;.
REVEL
Benign
0.17
Sift
Uncertain
0.025
.;.;D;.
Sift4G
Uncertain
0.014
D;D;D;D
Polyphen
0.016
B;.;B;.
Vest4
0.55
MutPred
0.47
Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);.;
MVP
0.32
MPC
0.94
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.43
gMVP
0.57

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: rs999134544; hg19: chr19-12848422; API