Variant 6-127515608-G-T 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_001400265.1(SOGA3):c.1007C>A(p.Pro336His) variant causes a missense change. The variant allele was found at a frequency of 0.0000331 in 1,421,562 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

SOGA3
NM_001400265.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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:

SOGA3-KIAA0408 (HGNC:):

SOGA3-KIAA0408 links:

Genome browser will be placed here

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=0.16302511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOGA3	NM_001400265.1 linkuse as main transcript	c.1007C>A	p.Pro336His	missense_variant	2/7	ENST00000525778.6	NP_001387194.1
SOGA3-KIAA0408	NR_174482.1 linkuse as main transcript	n.1852C>A		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SOGA3	ENST00000525778.6 linkuse as main transcript	c.1007C>A	p.Pro336His	missense_variant	2/7	5	NM_001400265.1	ENSP00000434570	P2
SOGA3	ENST00000465909.3 linkuse as main transcript	c.1007C>A	p.Pro336His	missense_variant	2/7	5		ENSP00000435559	A2
SOGA3	ENST00000703793.1 linkuse as main transcript	c.461C>A	p.Pro154His	missense_variant	1/5			ENSP00000515479

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000347

AC:

AN:

1269508

Hom.:

Cov.:

AF XY:

0.0000355

AC XY:

AN XY:

619132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000403

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:

0.0000420

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000185

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

Dec 19, 2022

The c.1007C>A (p.P336H) alteration is located in exon 2 (coding exon 1) of the SOGA3 gene. This alteration results from a C to A substitution at nucleotide position 1007, causing the proline (P) at amino acid position 336 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.059

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.084

T;T

Polyphen

0.0010

B;.

Vest4

0.35

MVP

0.16

ClinPred

0.27

GERP RS

4.5

Varity_R

0.14

gMVP

0.26

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