Variant 16-88686333-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000332281.6(SNAI3):c.74G>C(p.Arg25Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,611,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

SNAI3
ENST00000332281.6 missense, splice_region

Scores

Splicing: ADA: 0.00005227

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.327

Variant links:

Genes affected

SNAI3 (HGNC:18411): (snail family transcriptional repressor 3) SNAI3 is a member of the SNAIL gene family, named for the Drosophila snail gene, which plays roles in mesodermal formation during embryogenesis (Katoh and Katoh, 2003 [PubMed 12579345]).[supplied by OMIM, Apr 2009]

SNAI3 links:

SNAI3-AS1 (HGNC:28327): (SNAI3 antisense RNA 1)

SNAI3-AS1 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=0.036079556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAI3	NM_178310.4 linkuse as main transcript	c.74G>C	p.Arg25Thr	missense_variant, splice_region_variant	1/3	ENST00000332281.6	NP_840101.1
SNAI3-AS1	NR_024399.1 linkuse as main transcript	n.528-458C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAI3	ENST00000332281.6 linkuse as main transcript	c.74G>C	p.Arg25Thr	missense_variant, splice_region_variant	1/3	1	NM_178310.4	ENSP00000327968	P1
SNAI3-AS1	ENST00000563261.7 linkuse as main transcript	n.603-458C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000165

AC:

AN:

242166

Hom.:

AF XY:

0.000204

AC XY:

AN XY:

132548

show subpopulations

Gnomad AFR exome

AF:

0.000132

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:

0.000345

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000578

AC:

843

AN:

1458816

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

383

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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:

0.000719

Gnomad4 OTH exome

AF:

0.000681

GnomAD4 genome

AF:

0.000289

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000359

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000125

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000475

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 24, 2022

The c.74G>C (p.R25T) alteration is located in exon 1 (coding exon 1) of the SNAI3 gene. This alteration results from a G to C substitution at nucleotide position 74, causing the arginine (R) at amino acid position 25 to be replaced by a threonine (T). 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

0.31

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.016

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.89

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.030

Sift

Benign

0.62

Sift4G

Benign

0.40

Polyphen

0.012

Vest4

0.19

MVP

0.22

MPC

0.12

ClinPred

0.033

GERP RS

2.0

Varity_R

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000052

dbscSNV1_RF

Benign

0.0040

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