16-88681552-A-G

Position:

• chr16-88681552-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178310.4(SNAI3):​c.239T>C​(p.Leu80Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNAI3 NM_178310.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.448

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:):

ACMG classification

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=0.051850945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAI3	NM_178310.4	c.239T>C	p.Leu80Pro	missense_variant	2/3	ENST00000332281.6	NP_840101.1
SNAI3-AS1	NR_024399.1	n.528-5239A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAI3	ENST00000332281.6	c.239T>C	p.Leu80Pro	missense_variant	2/3	1	NM_178310.4	ENSP00000327968.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.239T>C (p.L80P) alteration is located in exon 2 (coding exon 2) of the SNAI3 gene. This alteration results from a T to C substitution at nucleotide position 239, causing the leucine (L) at amino acid position 80 to be replaced by a proline (P). 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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.78
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.49	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.040
Sift	Benign	0.35	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.085
MutPred		0.54		Loss of stability (P = 0.0102);
MVP		0.16
MPC		0.44
ClinPred		0.091	T
GERP RS		1.1
Varity_R		0.078

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88747960;