20-36793810-G-C

Variant names:

• chr20-36793810-G-C
• NM_080627.4:c.4272C>G

Variant summary

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

The NM_080627.4(MTCL2):​c.4272C>G​(p.Asp1424Glu) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTCL2 NM_080627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.789

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09578672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL2	NM_080627.4	c.4272C>G	p.Asp1424Glu	missense_variant	Exon 14 of 15	ENST00000237536.9	NP_542194.2
MTCL2	NM_199181.3	c.2993+565C>G		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.4272C>G	p.Asp1424Glu	missense_variant	Exon 14 of 15	5	NM_080627.4	ENSP00000237536.4
SOGA1	ENST00000279034.10	c.2993+565C>G		intron_variant	Intron 14 of 14	5		ENSP00000279034.5
SOGA1	ENST00000465671.1	n.3111C>G		non_coding_transcript_exon_variant	Exon 10 of 12	2		ENSP00000433939.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4272C>G (p.D1424E) alteration is located in exon 14 (coding exon 14) of the SOGA1 gene. This alteration results from a C to G substitution at nucleotide position 4272, causing the aspartic acid (D) at amino acid position 1424 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	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.80
Eigen	Benign	-0.11
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.12
MutPred		0.093		Gain of helix (P = 0.0854);
MVP		0.082
MPC		1.2
ClinPred		0.22	T
GERP RS		3.9
gMVP		0.25

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: chr20-35422213;