chr7-127686653-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014390.4(SND1):​c.119G>A​(p.Arg40His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SND1
NM_014390.4 missense

Scores

3
5
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22315335).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SND1NM_014390.4 linkuse as main transcriptc.119G>A p.Arg40His missense_variant 2/24 ENST00000354725.8 NP_055205.2
SND1XM_017011987.3 linkuse as main transcriptc.119G>A p.Arg40His missense_variant 2/17 XP_016867476.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SND1ENST00000354725.8 linkuse as main transcriptc.119G>A p.Arg40His missense_variant 2/241 NM_014390.4 ENSP00000346762 P1
SND1ENST00000461056.5 linkuse as main transcriptn.262G>A non_coding_transcript_exon_variant 2/44
SND1ENST00000463020.1 linkuse as main transcriptn.299G>A non_coding_transcript_exon_variant 2/22
SND1ENST00000468621.5 linkuse as main transcriptn.134G>A non_coding_transcript_exon_variant 2/54

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251288
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461854
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Teratoma Uncertain:1
Uncertain significance, no assertion criteria providedresearchMolecular ImmunoRheumatology UMRS_1109, Institut national de la santé et de la recherche médicaleJan 01, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.36
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.16
Sift
Benign
0.25
T
Sift4G
Benign
0.46
T
Polyphen
0.32
B
Vest4
0.57
MutPred
0.39
Loss of methylation at R40 (P = 0.0268);
MVP
0.37
MPC
0.82
ClinPred
0.78
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.55
gMVP
0.35

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: rs773076395; hg19: chr7-127326707; COSMIC: COSV61234632; API