Genetic Variant SND1:p.Ser3Phe (chr7-127652381-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014390.4(SND1):c.8C>T(p.Ser3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,597,684 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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SND1
NM_014390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Publications

1 publications found

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]

SND1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1308254).

BS2

High AC in GnomAdExome4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SND1	NM_014390.4 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 24	ENST00000354725.8	NP_055205.2	Q7KZF4A0A140VK49
SND1	XM_017011987.3 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 17		XP_016867476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SND1	ENST00000354725.8 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 24	1	NM_014390.4	ENSP00000346762.3		Q7KZF4
SND1	ENST00000463020.1 link	n.188C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152252

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000275

AC:

AN:

218440

AF XY:

0.0000339

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000307

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000491

AC:

AN:

1445432

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

717202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.0000239

AC:

AN:

41922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25666

East Asian (EAS)

AF:

0.000718

AC:

AN:

38998

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

1104740

Other (OTH)

AF:

0.000100

AC:

AN:

59760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.8C>T (p.S3F) alteration is located in exon 1 (coding exon 1) of the SND1 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a phenylalanine (F). 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

0.31

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

1.7

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

REVEL

Benign

0.037

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.010

Polyphen

0.68

Vest4

0.41

MutPred

0.27

Loss of phosphorylation at S3 (P = 0.011);

MVP

0.23

MPC

0.67

ClinPred

0.53

GERP RS

4.9

PromoterAI

-0.21

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.32

Mutation Taster

=83/17

polymorphism

(source)

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

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7-127652381-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over