chr20-36793574-C-T

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

Scores

7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MTCL2NM_080627.4 linkc.4508G>A p.Gly1503Glu missense_variant Exon 14 of 15 ENST00000237536.9 NP_542194.2 O94964-2
MTCL2NM_199181.3 linkc.2993+801G>A intron_variant Intron 14 of 14 NP_954650.2 O94964X6R3R3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOGA1ENST00000237536.9 linkc.4508G>A p.Gly1503Glu missense_variant Exon 14 of 15 5 NM_080627.4 ENSP00000237536.4 O94964-2
SOGA1ENST00000279034.10 linkc.2993+801G>A intron_variant Intron 14 of 14 5 ENSP00000279034.5 X6R3R3
SOGA1ENST00000465671.1 linkn.3347G>A non_coding_transcript_exon_variant Exon 10 of 12 2 ENSP00000433939.1 H0YDM2

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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
LINK: link

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; API