Genetic Variant SNAI1:p.Ala66Val (chr20-49983938-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005985.4(SNAI1):c.197C>T(p.Ala66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,613,428 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 128 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 132 hom. )

Consequence

SNAI1
NM_005985.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.607

Variant links:

Genes affected

SNAI1 (HGNC:11128): (snail family transcriptional repressor 1) The Drosophila embryonic protein snail is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. [provided by RefSeq, Jul 2008]

SNAI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001416713).

BP6

Variant 20-49983938-C-T is Benign according to our data. Variant chr20-49983938-C-T is described in ClinVar as [Benign]. Clinvar id is 769095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAI1	NM_005985.4 link	c.197C>T	p.Ala66Val	missense_variant	Exon 2 of 3	ENST00000244050.3	NP_005976.2	O95863

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAI1	ENST00000244050.3 link	c.197C>T	p.Ala66Val	missense_variant	Exon 2 of 3	1	NM_005985.4	ENSP00000244050.2		O95863

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3197

AN:

152108

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00664

AC:

1665

AN:

250582

Hom.:

AF XY:

0.00561

AC XY:

761

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00745

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00274

AC:

3998

AN:

1461202

Hom.:

132

Cov.:

AF XY:

0.00266

AC XY:

1933

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.0778

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00681

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.0211

AC:

3207

AN:

152226

Hom.:

128

Cov.:

AF XY:

0.0205

AC XY:

1524

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00747

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.0239

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0729

AC:

321

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00784

AC:

952

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.25

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.49

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.23

REVEL

Benign

0.11

Sift

Benign

0.45

Sift4G

Benign

0.52

Polyphen

0.0040

Vest4

0.036

MVP

0.11

MPC

0.59

ClinPred

0.0045

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.21

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