20-36794109-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_080627.4(SOGA1):​c.3973G>A​(p.Gly1325Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,551,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SOGA1
NM_080627.4 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48
Variant links:
Genes affected
SOGA1 (HGNC:16111): (microtubule crosslinking factor 2) Predicted to be involved in insulin receptor signaling pathway; negative regulation of gluconeogenesis; and regulation of autophagy. Located in extracellular space. [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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18188176).
BS2
High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SOGA1NM_080627.4 linkuse as main transcriptc.3973G>A p.Gly1325Arg missense_variant 14/15 ENST00000237536.9 NP_542194.2
SOGA1NM_199181.3 linkuse as main transcriptc.2993+266G>A intron_variant NP_954650.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SOGA1ENST00000237536.9 linkuse as main transcriptc.3973G>A p.Gly1325Arg missense_variant 14/155 NM_080627.4 ENSP00000237536 P2O94964-2
SOGA1ENST00000279034.10 linkuse as main transcriptc.2993+266G>A intron_variant 5 ENSP00000279034 A2
SOGA1ENST00000465671.1 linkuse as main transcriptc.2815G>A p.Gly939Arg missense_variant, NMD_transcript_variant 10/122 ENSP00000433939

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000643
AC:
1
AN:
155466
Hom.:
0
AF XY:
0.0000121
AC XY:
1
AN XY:
82552
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000921
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000114
AC:
16
AN:
1399078
Hom.:
0
Cov.:
31
AF XY:
0.0000130
AC XY:
9
AN XY:
690040
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.0000397
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000742
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000340

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 GeneticsNov 03, 2022The c.3973G>A (p.G1325R) alteration is located in exon 14 (coding exon 14) of the SOGA1 gene. This alteration results from a G to A substitution at nucleotide position 3973, causing the glycine (G) at amino acid position 1325 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
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
20
DANN
Uncertain
1.0
Eigen
Benign
0.085
Eigen_PC
Benign
0.095
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
0.65
D;D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.97
N
REVEL
Benign
0.15
Sift
Benign
0.044
D
Sift4G
Benign
0.067
T
Vest4
0.27
MutPred
0.17
Gain of methylation at G1325 (P = 0.0189);
MVP
0.20
MPC
2.3
ClinPred
0.58
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
gMVP
0.40

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: rs969320971; hg19: chr20-35422512; API