chr6-127475659-G-C

Position:

• chr6-127475659-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001400265.1(SOGA3):​c.2367C>G​(p.Ile789Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOGA3 NM_001400265.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

Genes affected

SOGA3 (HGNC:21494): (MTCL family member 3) Predicted to be involved in regulation of autophagy. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SOGA3-KIAA0408 (HGNC:):

ACMG classification

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=0.15808144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOGA3	NM_001400265.1	c.2367C>G	p.Ile789Met	missense_variant	6/7	ENST00000525778.6	NP_001387194.1
SOGA3-KIAA0408	NR_174482.1	n.3212C>G		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOGA3	ENST00000525778.6	c.2367C>G	p.Ile789Met	missense_variant	6/7	5	NM_001400265.1	ENSP00000434570	P2
SOGA3	ENST00000465909.3	c.2367C>G	p.Ile789Met	missense_variant	6/7	5		ENSP00000435559	A2
SOGA3	ENST00000703793.1	c.1821C>G	p.Ile607Met	missense_variant	5/5			ENSP00000515479

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.2367C>G (p.I789M) alteration is located in exon 6 (coding exon 5) of the SOGA3 gene. This alteration results from a C to G substitution at nucleotide position 2367, causing the isoleucine (I) at amino acid position 789 to be replaced by a methionine (M). 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	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.13
Sift	Benign	0.055	T;T
Sift4G	Uncertain	0.027	D;D
Polyphen		0.97	D;.
Vest4		0.21
MutPred		0.28		Gain of catalytic residue at I789 (P = 0.0428);Gain of catalytic residue at I789 (P = 0.0428);
MVP		0.067
ClinPred		0.82	D
GERP RS		2.2
Varity_R		0.12
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-127796804;