6-127475361-T-C

Position:

• chr6-127475361-T-C

Variant summary

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

The NM_001400265.1(MTCL3):​c.2665A>G​(p.Ile889Val) variant causes a missense change involving the alteration of a 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: MTCL3 NM_001400265.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

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]

ENSG00000255330 (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=0.19212553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCL3	NM_001400265.1	c.2665A>G	p.Ile889Val	missense_variant	6/7		NP_001387194.1
SOGA3-KIAA0408	NR_174482.1	n.3510A>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.2665A>G	p.Ile889Val	missense_variant	6/7	5		ENSP00000434570.1
ENSG00000255330	ENST00000481848.6	n.2665A>G		non_coding_transcript_exon_variant	6/12	5		ENSP00000455908.1

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

Nov 10, 2022

The c.2665A>G (p.I889V) alteration is located in exon 6 (coding exon 5) of the SOGA3 gene. This alteration results from a A to G substitution at nucleotide position 2665, causing the isoleucine (I) at amino acid position 889 to be replaced by a valine (V). 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	0.22
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	0.019
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.11
Sift	Benign	0.087	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.063	B;.
Vest4		0.42
MutPred		0.21		Loss of catalytic residue at I889 (P = 0.0674);Loss of catalytic residue at I889 (P = 0.0674);
MVP		0.030
ClinPred		0.50	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.87

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: chr6-127796506;