20-49983133-C-G

Variant names:

• chr20-49983133-C-G
• rs761598892
• NM_005985.4:c.74C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005985.4(SNAI1):​c.74C>G​(p.Ser25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SNAI1 NM_005985.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.602
• Publications: 1 publications found

Genes affected

SNAI1 (HGNC:11128): (snail family transcriptional repressor 1) The Drosophila embryonic protein snail is a zinc finger transcriptional repressor which downregulates the expression of ectodermal genes within the mesoderm. The nuclear protein encoded by this gene is structurally similar to the Drosophila snail protein, and is also thought to be critical for mesoderm formation in the developing embryo. At least two variants of a similar processed pseudogene have been found on chromosome 2. [provided by RefSeq, Jul 2008]

SNAI1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08743045).
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005985.4. 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
	SNAI1	NM_005985.4	MANE Select	c.74C>G	p.Ser25Cys	missense	Exon 1 of 3	NP_005976.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAI1	ENST00000244050.3	TSL:1 MANE Select	c.74C>G	p.Ser25Cys	missense	Exon 1 of 3	ENSP00000244050.2	O95863

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152096 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250256 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461076 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 726850

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.000134 AC: 6 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

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

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111484

Other (OTH) AF: 0.000116 AC: 7 AN: 60352

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152096 Hom.: 0 Cov.: 28 AF XY: 0.0000404 AC XY: 3 AN XY: 74286

African (AFR) AF: 0.0000483 AC: 2 AN: 41422

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00144 AC: 3 AN: 2086

Alfa AF: 0.0000852 Hom.: 0

Bravo AF: 0.000144

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Benign	0.67
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.60
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.029
Sift	Benign	0.15	T
Sift4G	Uncertain	0.028	D
Polyphen		0.51	P
Vest4		0.41
MutPred		0.37		Loss of phosphorylation at S25 (P = 0.0508)
MVP		0.15
MPC		0.98
ClinPred		0.11	T
GERP RS		2.4
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.32
Mutation Taster		=76/24	polymorphism

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: rs761598892; hg19: chr20-48599670;