chr6-127515035-C-T

Position:

• chr6-127515035-C-T

Variant summary

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

The NM_001400265.1(SOGA3):​c.1114G>A​(p.Glu372Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOGA3 NM_001400265.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOGA3	NM_001400265.1	c.1114G>A	p.Glu372Lys	missense_variant	3/7	ENST00000525778.6	NP_001387194.1
SOGA3-KIAA0408	NR_174482.1	n.1959G>A		non_coding_transcript_exon_variant	3/13
LOC107986642	XR_001744337.2	n.1919C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOGA3	ENST00000525778.6	c.1114G>A	p.Glu372Lys	missense_variant	3/7	5	NM_001400265.1	ENSP00000434570	P2
SOGA3	ENST00000465909.3	c.1114G>A	p.Glu372Lys	missense_variant	3/7	5		ENSP00000435559	A2
SOGA3	ENST00000703793.1	c.568G>A	p.Glu190Lys	missense_variant	2/5			ENSP00000515479

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Feb 28, 2023

The c.1114G>A (p.E372K) alteration is located in exon 3 (coding exon 2) of the SOGA3 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the glutamic acid (E) at amino acid position 372 to be replaced by a lysine (K). 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	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.37		Gain of ubiquitination at E372 (P = 0.0066);Gain of ubiquitination at E372 (P = 0.0066);
MVP		0.11
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.50

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: chr6-127836180;