16-88681450-A-G

Position:

• chr16-88681450-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178310.4(SNAI3):​c.341T>C​(p.Leu114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNAI3 NM_178310.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAI3	NM_178310.4	c.341T>C	p.Leu114Pro	missense_variant	2/3	ENST00000332281.6	NP_840101.1
SNAI3-AS1	NR_024399.1	n.528-5341A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAI3	ENST00000332281.6	c.341T>C	p.Leu114Pro	missense_variant	2/3	1	NM_178310.4	ENSP00000327968	P1
SNAI3-AS1	ENST00000563261.7	n.603-5341A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449744 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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 26, 2023

The c.341T>C (p.L114P) 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 341, causing the leucine (L) at amino acid position 114 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	0.90
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.21
Sift	Benign	0.082	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.67		Gain of disorder (P = 0.012);
MVP		0.58
MPC		0.44
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.25

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

Other links and lift over

dbSNP: rs367570205; hg19: chr16-88747858;