Genetic Variant NM_080627.4:c.4408G>A (chr20-36793674-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080627.4(MTCL2):c.4408G>A(p.Gly1470Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,397,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

MTCL2
NM_080627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Variant links:

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]

MTCL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32238704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL2	NM_080627.4 link	c.4408G>A	p.Gly1470Ser	missense_variant	Exon 14 of 15	ENST00000237536.9	NP_542194.2	O94964-2
MTCL2	NM_199181.3 link	c.2993+701G>A		intron_variant	Intron 14 of 14		NP_954650.2	O94964X6R3R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SOGA1	ENST00000237536.9 link	c.4408G>A	p.Gly1470Ser	missense_variant	Exon 14 of 15	5	NM_080627.4	ENSP00000237536.4	O94964-2
SOGA1	ENST00000279034.10 link	c.2993+701G>A		intron_variant	Intron 14 of 14	5		ENSP00000279034.5	X6R3R3
SOGA1	ENST00000465671.1 link	n.3247G>A		non_coding_transcript_exon_variant	Exon 10 of 12	2		ENSP00000433939.1	H0YDM2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000263

AC:

AN:

152174

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

81044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000919

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000507

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000930

AC:

AN:

1397720

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

689452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4408G>A (p.G1470S) 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 4408, causing the glycine (G) at amino acid position 1470 to be replaced by a serine (S). 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

-0.20

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.090

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.035

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

REVEL

Benign

0.19

Sift

Benign

0.15

Sift4G

Benign

0.44

Vest4

0.58

MutPred

0.15

Gain of phosphorylation at G1470 (P = 0.0797);

MVP

0.10

MPC

2.2

ClinPred

0.23

GERP RS

3.9

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over