7-127686728-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_014390.4(SND1):c.194C>T(p.Ala65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,182 control chromosomes in the GnomAD database, including 3 homozygotes. 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: 𝑓 0.0010 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: SND1 NM_014390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

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 Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SND1
• BP4: Computational evidence support a benign effect (MetaRNN=0.005766958).
• BS2: High AC in GnomAd at 156 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SND1	NM_014390.4	c.194C>T	p.Ala65Val	missense_variant	2/24	ENST00000354725.8
SND1	XM_017011987.3	c.194C>T	p.Ala65Val	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SND1	ENST00000354725.8	c.194C>T	p.Ala65Val	missense_variant	2/24	1	NM_014390.4	P1
SND1	ENST00000461056.5	n.337C>T		non_coding_transcript_exon_variant	2/4	4
SND1	ENST00000463020.1	n.374C>T		non_coding_transcript_exon_variant	2/2	2
SND1	ENST00000468621.5	n.209C>T		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 156 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000832 AC: 209 AN: 251350 Hom.: 0 AF XY: 0.000847 AC XY: 115 AN XY: 135836

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.00108 AC: 1579 AN: 1461842 Hom.: 2 Cov.: 30 AF XY: 0.00108 AC XY: 788 AN XY: 727216

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000693

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000591

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.00102 AC: 156 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.000980 AC XY: 73 AN XY: 74494

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00117 Hom.: 1

Bravo AF: 0.00116

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.000857 AC: 104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00255

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 04, 2022

The c.194C>T (p.A65V) alteration is located in exon 2 (coding exon 2) of the SND1 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the alanine (A) at amino acid position 65 to be replaced by a valine (V). 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	0.078
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.024
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.19	B
Vest4		0.28
MVP		0.30
MPC		0.63
ClinPred		0.0090	T
GERP RS		0.90
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.18
gMVP		0.25

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: rs144637656; hg19: chr7-127326782;