Variant 6-127515591-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001400265.1(MTCL3):c.1024C>G(p.His342Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,434,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

MTCL3
NM_001400265.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0140

Variant links:

Genes affected

SOGA3 (HGNC:21494): (MTCL family member 3) Predicted to be involved in regulation of autophagy. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SOGA3 links:

ENSG00000255330 (HGNC:):

ENSG00000255330 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059136212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCL3	NM_001400265.1 linkuse as main transcript	c.1024C>G	p.His342Asp	missense_variant	2/7		NP_001387194.1
SOGA3-KIAA0408	NR_174482.1 linkuse as main transcript	n.1869C>G		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
SOGA3	ENST00000525778.6 linkuse as main transcript	c.1024C>G	p.His342Asp	missense_variant	2/7	5	ENSP00000434570.1	Q5TF21
ENSG00000255330	ENST00000481848.6 linkuse as main transcript	n.1024C>G		non_coding_transcript_exon_variant	2/12	5	ENSP00000455908.1
SOGA3	ENST00000465909.3 linkuse as main transcript	c.1024C>G	p.His342Asp	missense_variant	2/7	5	ENSP00000435559.1	E9PJP2
SOGA3	ENST00000703793.1 linkuse as main transcript	c.475C>G	p.His159Asp	missense_variant	1/5		ENSP00000515479.1	A0A994J4H7

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000182

AC:

AN:

54850

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

28378

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000382

Gnomad OTH exome

AF:

0.000942

GnomAD4 exome

AF:

0.000312

AC:

400

AN:

1282108

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

193

AN XY:

626832

show subpopulations

Gnomad4 AFR exome

AF:

0.000159

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000433

Gnomad4 NFE exome

AF:

0.000370

Gnomad4 OTH exome

AF:

0.000171

GnomAD4 genome

AF:

0.000256

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.0000966

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

Jun 26, 2023

The c.1024C>G (p.H342D) alteration is located in exon 2 (coding exon 1) of the SOGA3 gene. This alteration results from a C to G substitution at nucleotide position 1024, causing the histidine (H) at amino acid position 342 to be replaced by an aspartic acid (D). 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.62

T;T

Polyphen

0.012

B;.

Vest4

0.27

MVP

0.095

ClinPred

0.018

GERP RS

3.6

Varity_R

0.18

gMVP

0.24

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