20-49983938-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 128 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 132 hom. )

Consequence

SNAI1
NM_005985.4 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.607
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNAI1NM_005985.4 linkc.197C>T p.Ala66Val missense_variant Exon 2 of 3 ENST00000244050.3 NP_005976.2 O95863

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNAI1ENST00000244050.3 linkc.197C>T p.Ala66Val missense_variant Exon 2 of 3 1 NM_005985.4 ENSP00000244050.2 O95863

Frequencies

GnomAD3 genomes
AF:
0.0210
AC:
3197
AN:
152108
Hom.:
128
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00664
AC:
1665
AN:
250582
Hom.:
66
AF XY:
0.00561
AC XY:
761
AN XY:
135540
show subpopulations
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 SAS exome
AF:
0.00745
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0778
Gnomad4 AMR exome
AF:
0.00398
Gnomad4 ASJ exome
AF:
0.000306
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00681
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000203
Gnomad4 OTH exome
AF:
0.00573
GnomAD4 genome
AF:
0.0211
AC:
3207
AN:
152226
Hom.:
128
Cov.:
32
AF XY:
0.0205
AC XY:
1524
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0720
Gnomad4 AMR
AF:
0.00784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00747
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0133
Alfa
AF:
0.00227
Hom.:
5
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

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 13, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34261470; hg19: chr20-48600475; API