NM_178310.4:c.341T>C

Variant names:

• chr16-88681450-A-G
• rs367570205
• NM_178310.4:c.341T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 2 ACMG points.

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

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.341T>C	p.Leu114Pro	missense	Exon 2 of 3	NP_840101.1	Q3KNW1
	SNAI3-AS1	NR_024399.1		n.528-5341A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAI3	ENST00000332281.6	TSL:1 MANE Select	c.341T>C	p.Leu114Pro	missense	Exon 2 of 3	ENSP00000327968.5	Q3KNW1
	SNAI3-AS1	ENST00000563261.7	TSL:1	n.603-5341A>G		intron	N/A
	SNAI3-AS1	ENST00000687428.2		n.369-5341A>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.00 AC: 0 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25660

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 85330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103554

Other (OTH) AF: 0.00 AC: 0 AN: 59736

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	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
PhyloP100		1.9
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

Other links and lift over

dbSNP: rs367570205; hg19: chr16-88747858;