16-88681391-C-G

Variant names:

• chr16-88681391-C-G
• rs770113114
• NM_178310.4:c.400G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178310.4(SNAI3):​c.400G>C​(p.Gly134Arg) 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. 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. G134W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNAI3 NM_178310.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054507732).

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.400G>C	p.Gly134Arg	missense	Exon 2 of 3	NP_840101.1	Q3KNW1
	SNAI3-AS1	NR_024399.1		n.528-5400C>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.400G>C	p.Gly134Arg	missense	Exon 2 of 3	ENSP00000327968.5	Q3KNW1
	SNAI3-AS1	ENST00000563261.7	TSL:1	n.603-5400C>G		intron	N/A
	SNAI3-AS1	ENST00000687428.2		n.369-5400C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.47
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.58
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.0050
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.27		Gain of solvent accessibility (P = 0.019)
MVP		0.095
MPC		0.097
ClinPred		0.074	T
GERP RS		-2.9
Varity_R		0.060

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: rs770113114; hg19: chr16-88747799; COSMIC: COSV60003212; COSMIC: COSV60003212;