chr16-88681339-C-A

Variant names:

• chr16-88681339-C-A
• rs766794910
• NM_178310.4:c.452G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178310.4(SNAI3):​c.452G>T​(p.Gly151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNAI3 NM_178310.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

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

ACMG classification

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=0.091893554).

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.452G>T	p.Gly151Val	missense	Exon 2 of 3	NP_840101.1	Q3KNW1
	SNAI3-AS1	NR_024399.1		n.528-5452C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAI3	ENST00000332281.6	TSL:1 MANE Select	c.452G>T	p.Gly151Val	missense	Exon 2 of 3	ENSP00000327968.5	Q3KNW1
	SNAI3-AS1	ENST00000563261.7	TSL:1	n.603-5452C>A		intron	N/A
	SNAI3-AS1	ENST00000687428.2		n.369-5452C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460604 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726584

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111706

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.5
DANN	Benign	0.64
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.090
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.55		Loss of disorder (P = 0.0223)
MVP		0.18
MPC		0.10
ClinPred		0.066	T
GERP RS		3.7
Varity_R		0.065

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

Other links and lift over

dbSNP: rs766794910; hg19: chr16-88747747;