NM_005985.4:c.197C>T

Variant names:

• chr20-49983938-C-T
• rs34261470
• NM_005985.4:c.197C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005985.4(SNAI1):​c.197C>T​(p.Ala66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,613,428 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (128 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (132 hom.)
• Consequence: SNAI1 NM_005985.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.607
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001416713).
• BP6: Variant 20-49983938-C-T is Benign according to our data. Variant chr20-49983938-C-T is described in ClinVar as Benign. ClinVar VariationId is 769095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

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.197C>T	p.Ala66Val	missense	Exon 2 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.197C>T	p.Ala66Val	missense	Exon 2 of 3	ENSP00000244050.2	O95863

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3197 AN: 152108 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00664 AC: 1665 AN: 250582 AF XY: 0.00561

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00274 AC: 3998 AN: 1461202 Hom.: 132 Cov.: 32 AF XY: 0.00266 AC XY: 1933 AN XY: 726978

African (AFR) AF: 0.0778 AC: 2606 AN: 33478

American (AMR) AF: 0.00398 AC: 178 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00681 AC: 587 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52762

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5766

European-Non Finnish (NFE) AF: 0.000203 AC: 226 AN: 1112002

Other (OTH) AF: 0.00573 AC: 346 AN: 60386

GnomAD4 genome AF: 0.0211 AC: 3207 AN: 152226 Hom.: 128 Cov.: 32 AF XY: 0.0205 AC XY: 1524 AN XY: 74428

African (AFR) AF: 0.0720 AC: 2993 AN: 41548

American (AMR) AF: 0.00784 AC: 120 AN: 15306

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

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

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67996

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.0123 Hom.: 45

Bravo AF: 0.0239

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0729 AC: 321

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00784 AC: 952

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.61
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.11
Sift	Benign	0.45	T
Sift4G	Benign	0.52	T
Polyphen		0.0040	B
Vest4		0.036
MVP		0.11
MPC		0.59
ClinPred		0.0045	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.21
Mutation Taster		=95/5	polymorphism (auto)

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: rs34261470; hg19: chr20-48600475;