7-127701242-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_014390.4(SND1):c.508T>G(p.Ser170Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,918 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: SND1 NM_014390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SND1
• BP4: Computational evidence support a benign effect (MetaRNN=0.07187718).
• BS2: High AC in GnomAd at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SND1	NM_014390.4	c.508T>G	p.Ser170Ala	missense_variant	5/24	ENST00000354725.8
SND1	XM_017011987.3	c.508T>G	p.Ser170Ala	missense_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SND1	ENST00000354725.8	c.508T>G	p.Ser170Ala	missense_variant	5/24	1	NM_014390.4	P1
SND1	ENST00000483503.5	n.403T>G		non_coding_transcript_exon_variant	4/6	5
SND1	ENST00000492772.1	n.315T>G		non_coding_transcript_exon_variant	4/6	4
SND1	ENST00000468621.5			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000175 AC: 44 AN: 251328 Hom.: 0 AF XY: 0.000214 AC XY: 29 AN XY: 135812

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000463

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: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000163 AC: 238 AN: 1461806 Hom.: 2 Cov.: 31 AF XY: 0.000169 AC XY: 123 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000470

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: 0.000174

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74298

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000238 Hom.: 0

Bravo AF: 0.000283

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2022

The c.508T>G (p.S170A) 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 508, causing the serine (S) at amino acid position 170 to be replaced by an alanine (A). 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	0.061
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	15
Dann	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.82	D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.021
Sift	Benign	0.55	T
Sift4G	Benign	0.54	T
Polyphen		0.0010	B
Vest4		0.25
MVP		0.39
MPC		0.51
ClinPred		0.025	T
GERP RS		3.4
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.31

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

Other links and lift over

dbSNP: rs144027003; hg19: chr7-127341296;