chr20-36793574-C-T

Variant names:

• chr20-36793574-C-T
• NM_080627.4:c.4508G>A

Variant summary

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

The NM_080627.4(MTCL2):​c.4508G>A​(p.Gly1503Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,318 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MTCL2 NM_080627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08

Genes affected

MTCL2 (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]

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 rank	MANE	Protein	UniProt
MTCL2	NM_080627.4	c.4508G>A	p.Gly1503Glu	missense_variant	Exon 14 of 15	ENST00000237536.9	NP_542194.2
MTCL2	NM_199181.3	c.2993+801G>A		intron_variant	Intron 14 of 14		NP_954650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOGA1	ENST00000237536.9	c.4508G>A	p.Gly1503Glu	missense_variant	Exon 14 of 15	5	NM_080627.4	ENSP00000237536.4
SOGA1	ENST00000279034.10	c.2993+801G>A		intron_variant	Intron 14 of 14	5		ENSP00000279034.5
SOGA1	ENST00000465671.1	n.3347G>A		non_coding_transcript_exon_variant	Exon 10 of 12	2		ENSP00000433939.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399318 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4508G>A (p.G1503E) 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 4508, causing the glycine (G) at amino acid position 1503 to be replaced by a glutamic acid (E). 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	-0.0033	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.076	T
Sift4G	Benign	0.083	T
Vest4		0.61
MutPred		0.24		Gain of solvent accessibility (P = 0.012);
MVP		0.068
MPC		2.5
ClinPred		0.93	D
GERP RS		5.0
gMVP		0.66

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: chr20-35421977;