Variant 20-36794213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080627.4(MTCL2):c.3869C>T(p.Ser1290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000911 in 1,547,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

MTCL2
NM_080627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014761299).

BS2

High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCL2	NM_080627.4 linkuse as main transcript	c.3869C>T	p.Ser1290Leu	missense_variant	14/15	ENST00000237536.9	NP_542194.2	O94964-2
MTCL2	NM_199181.3 linkuse as main transcript	c.2993+162C>T		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.3869C>T	p.Ser1290Leu	missense_variant	14/15	5	NM_080627.4	ENSP00000237536.4	O94964-2
SOGA1	ENST00000279034.10 linkuse as main transcript	c.2993+162C>T		intron_variant		5		ENSP00000279034.5	X6R3R3
SOGA1	ENST00000465671.1 linkuse as main transcript	n.2708C>T		non_coding_transcript_exon_variant	10/12	2		ENSP00000433939.1	H0YDM2

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000613

AC:

AN:

154934

Hom.:

AF XY:

0.000597

AC XY:

AN XY:

82052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.0000443

Gnomad FIN exome

AF:

0.000658

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000461

GnomAD4 exome

AF:

0.000925

AC:

1290

AN:

1394832

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

637

AN XY:

687004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000952

Gnomad4 AMR exome

AF:

0.000197

Gnomad4 ASJ exome

AF:

0.0000798

Gnomad4 EAS exome

AF:

0.0000561

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.000793

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152348

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.000703

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000374

AC:

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

Aug 10, 2021

The c.3869C>T (p.S1290L) alteration is located in exon 14 (coding exon 14) of the SOGA1 gene. This alteration results from a C to T substitution at nucleotide position 3869, causing the serine (S) at amino acid position 1290 to be replaced by a leucine (L). 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

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Benign

0.0094

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Uncertain

0.029

Sift4G

Uncertain

0.031

Vest4

0.065

MVP

0.20

MPC

0.97

ClinPred

0.045

GERP RS

5.3

gMVP

0.17

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