dbSNP rs138632824: SNAI3:p.Arg99Leu (chr16-88681495-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_178310.4(SNAI3):c.296G>T(p.Arg99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,552,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SNAI3
NM_178310.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

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=0.059211224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAI3	NM_178310.4 link	c.296G>T	p.Arg99Leu	missense_variant	Exon 2 of 3	ENST00000332281.6	NP_840101.1	Q3KNW1
SNAI3-AS1	NR_024399.1 link	n.528-5296C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAI3	ENST00000332281.6 link	c.296G>T	p.Arg99Leu	missense_variant	Exon 2 of 3	1	NM_178310.4	ENSP00000327968.5		Q3KNW1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000908

AC:

AN:

209226

Hom.:

AF XY:

0.0000896

AC XY:

AN XY:

111622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000518

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:

0.0000209

Gnomad OTH exome

AF:

0.000408

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1400668

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

687884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000434

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:

0.00000372

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000248

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.5

DANN

Benign

0.96

DEOGEN2

Benign

0.038

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.50

M_CAP

Benign

0.014

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Benign

0.035

Sift

Benign

0.14

Sift4G

Benign

0.76

Polyphen

0.029

Vest4

0.26

MutPred

0.49

Loss of disorder (P = 0.0457);

MVP

0.27

MPC

0.10

ClinPred

0.043

GERP RS

1.4

Varity_R

0.061

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over