7-127652393-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014390.4(SND1):​c.20G>A​(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SND1
NM_014390.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
SND1 (HGNC:30646): (staphylococcal nuclease and tudor domain containing 1) This gene encodes a transcriptional co-activator that interacts with the acidic domain of Epstein-Barr virus nuclear antigen 2 (EBNA 2), a transcriptional activator that is required for B-lymphocyte transformation. Other transcription factors that interact with this protein are signal transducers and activators of transcription, STATs. This protein is also thought to be essential for normal cell growth. A similar protein in mammals and other organisms is a component of the RNA-induced silencing complex (RISC). [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29738793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SND1NM_014390.4 linkuse as main transcriptc.20G>A p.Ser7Asn missense_variant 1/24 ENST00000354725.8 NP_055205.2
SND1XM_017011987.3 linkuse as main transcriptc.20G>A p.Ser7Asn missense_variant 1/17 XP_016867476.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SND1ENST00000354725.8 linkuse as main transcriptc.20G>A p.Ser7Asn missense_variant 1/241 NM_014390.4 ENSP00000346762 P1
SND1ENST00000463020.1 linkuse as main transcriptn.200G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000914
AC:
2
AN:
218752
Hom.:
0
AF XY:
0.0000169
AC XY:
2
AN XY:
118580
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000363
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000102
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1446644
Hom.:
0
Cov.:
30
AF XY:
0.00000279
AC XY:
2
AN XY:
717940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2022The c.20G>A (p.S7N) alteration is located in exon 1 (coding exon 1) of the SND1 gene. This alteration results from a G to A substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.017
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
0.96
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.069
Sift
Benign
0.34
T
Sift4G
Benign
0.38
T
Polyphen
0.27
B
Vest4
0.57
MutPred
0.13
Loss of glycosylation at S7 (P = 0.0028);
MVP
0.49
MPC
0.57
ClinPred
0.48
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.33

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: rs940214396; hg19: chr7-127292447; API