Variant 20-36793883-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080627.4(MTCL2):c.4199A>G(p.His1400Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,398,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MTCL2
NM_080627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18860266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCL2	NM_080627.4 linkuse as main transcript	c.4199A>G	p.His1400Arg	missense_variant	14/15	ENST00000237536.9	NP_542194.2	O94964-2
MTCL2	NM_199181.3 linkuse as main transcript	c.2993+492A>G		intron_variant			NP_954650.2	O94964X6R3R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOGA1	ENST00000237536.9 linkuse as main transcript	c.4199A>G	p.His1400Arg	missense_variant	14/15	5	NM_080627.4	ENSP00000237536.4	O94964-2
SOGA1	ENST00000279034.10 linkuse as main transcript	c.2993+492A>G		intron_variant		5		ENSP00000279034.5	X6R3R3
SOGA1	ENST00000465671.1 linkuse as main transcript	n.3038A>G		non_coding_transcript_exon_variant	10/12	2		ENSP00000433939.1	H0YDM2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000653

AC:

AN:

153092

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1398056

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689608

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:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000427

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

The c.4199A>G (p.H1400R) alteration is located in exon 14 (coding exon 14) of the SOGA1 gene. This alteration results from a A to G substitution at nucleotide position 4199, causing the histidine (H) at amino acid position 1400 to be replaced by an arginine (R). 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

-0.18

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.024

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.087

Sift

Benign

0.15

Sift4G

Benign

0.20

Vest4

0.18

MutPred

0.27

Gain of MoRF binding (P = 0.0041);

MVP

0.11

MPC

1.3

ClinPred

0.38

GERP RS

4.9

gMVP

0.46

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