Genetic Variant SNAI3:p.Asp94His (chr16-88681511-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178310.4(SNAI3):c.280G>C(p.Asp94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. D94N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SNAI3
NM_178310.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.074552536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178310.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAI3	NM_178310.4	MANE Select	c.280G>C	p.Asp94His	missense	Exon 2 of 3	NP_840101.1	Q3KNW1
	SNAI3-AS1	NR_024399.1		n.528-5280C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAI3	ENST00000332281.6	TSL:1 MANE Select	c.280G>C	p.Asp94His	missense	Exon 2 of 3	ENSP00000327968.5	Q3KNW1
SNAI3-AS1	ENST00000563261.7	TSL:1	n.603-5280C>G		intron	N/A
SNAI3-AS1	ENST00000687428.2		n.369-5280C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000151

AC:

AN:

198246

AF XY:

0.0000190

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1388434

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31682

American (AMR)

AF:

0.00

AC:

AN:

37232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21554

East Asian (EAS)

AF:

0.00

AC:

AN:

38820

South Asian (SAS)

AF:

0.0000396

AC:

AN:

75826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070696

Other (OTH)

AF:

0.00

AC:

AN:

57088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.033

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.39

M_CAP

Benign

0.0056

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

0.14

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

REVEL

Benign

0.033

Sift

Benign

0.14

Sift4G

Benign

0.26

Polyphen

0.0060

Vest4

0.072

MutPred

0.46

Gain of helix (P = 0.005)

MVP

0.23

MPC

0.45

ClinPred

0.086

GERP RS

3.1

Varity_R

0.035

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over