chr7-127701188-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014390.4(SND1):ā€‹c.454T>Gā€‹(p.Cys152Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

SND1
NM_014390.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22536305).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SND1NM_014390.4 linkuse as main transcriptc.454T>G p.Cys152Gly missense_variant 5/24 ENST00000354725.8 NP_055205.2
SND1XM_017011987.3 linkuse as main transcriptc.454T>G p.Cys152Gly missense_variant 5/17 XP_016867476.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SND1ENST00000354725.8 linkuse as main transcriptc.454T>G p.Cys152Gly missense_variant 5/241 NM_014390.4 ENSP00000346762 P1
SND1ENST00000468621.5 linkuse as main transcriptn.469T>G non_coding_transcript_exon_variant 5/54
SND1ENST00000483503.5 linkuse as main transcriptn.349T>G non_coding_transcript_exon_variant 4/65
SND1ENST00000492772.1 linkuse as main transcriptn.261T>G non_coding_transcript_exon_variant 4/64

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251232
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135758
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461782
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJan 19, 2024The c.454T>G (p.C152G) alteration is located in exon 5 (coding exon 5) of the SND1 gene. This alteration results from a T to G substitution at nucleotide position 454, causing the cysteine (C) at amino acid position 152 to be replaced by a glycine (G). 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
0.15
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.26
T
Eigen
Benign
-0.071
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.97
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.18
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.010
B
Vest4
0.49
MutPred
0.50
Loss of stability (P = 0.0421);
MVP
0.31
MPC
0.86
ClinPred
0.64
D
GERP RS
6.2
Varity_R
0.76
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs777713697; hg19: chr7-127341242; API