chr17-46929558-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004287.5(GOSR2):āc.68A>Gā(p.Glu23Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,562,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000021 ( 0 hom. )
Consequence
GOSR2
NM_004287.5 missense
NM_004287.5 missense
Scores
2
8
3
Clinical Significance
Conservation
PhyloP100: 8.97
Genes affected
GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GOSR2 | NM_004287.5 | c.68A>G | p.Glu23Gly | missense_variant | 2/6 | ENST00000640051.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GOSR2 | ENST00000640051.2 | c.68A>G | p.Glu23Gly | missense_variant | 2/6 | 1 | NM_004287.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251204Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135784
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GnomAD4 exome AF: 0.0000206 AC: 29AN: 1409960Hom.: 0 Cov.: 25 AF XY: 0.0000227 AC XY: 16AN XY: 704712
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74440
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 23 of the GOSR2 protein (p.Glu23Gly). This variant is present in population databases (rs200071814, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with GOSR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 405438). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;.;D;D;.;D;D;D;D;D;D;.;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.45, 0.45
.;.;.;B;.;.;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
0.93, 0.94, 0.90, 0.94
MutPred
Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);.;Loss of stability (P = 0.0545);.;.;.;Loss of stability (P = 0.0545);Loss of stability (P = 0.0545);.;.;.;.;.;
MVP
0.70
MPC
0.53
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at