NM_014390.4:c.2110+381C>T

Variant names:

• chr7-128081882-C-T
• rs73721294
• NM_014390.4:c.2110+381C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014390.4(SND1):​c.2110+381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 539,510 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (103 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (25 hom.)
• Consequence: SND1 NM_014390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 6 publications found

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]

MIR593 (HGNC:32849): (microRNA 593) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014390.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SND1	NM_014390.4	MANE Select	c.2110+381C>T		intron	N/A	NP_055205.2
	MIR593	NR_030324.1		n.22C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SND1	ENST00000354725.8	TSL:1 MANE Select	c.2110+381C>T		intron	N/A	ENSP00000346762.3
	SND1	ENST00000903603.1		c.2293+381C>T		intron	N/A	ENSP00000573662.1
	SND1	ENST00000915268.1		c.2200+381C>T		intron	N/A	ENSP00000585327.1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2839 AN: 152182 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

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: 0.000118

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00500 AC: 1256 AN: 251058 AF XY: 0.00366

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00237 AC: 919 AN: 387210 Hom.: 25 Cov.: 0 AF XY: 0.00184 AC XY: 405 AN XY: 220170

African (AFR) AF: 0.0666 AC: 715 AN: 10728

American (AMR) AF: 0.00310 AC: 113 AN: 36426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11956

East Asian (EAS) AF: 0.00 AC: 0 AN: 13516

South Asian (SAS) AF: 0.000120 AC: 8 AN: 66800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32512

Middle Eastern (MID) AF: 0.00140 AC: 4 AN: 2862

European-Non Finnish (NFE) AF: 0.000123 AC: 24 AN: 195388

Other (OTH) AF: 0.00323 AC: 55 AN: 17022

GnomAD4 genome AF: 0.0187 AC: 2846 AN: 152300 Hom.: 103 Cov.: 33 AF XY: 0.0177 AC XY: 1321 AN XY: 74480

African (AFR) AF: 0.0649 AC: 2697 AN: 41542

American (AMR) AF: 0.00771 AC: 118 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00927 Hom.: 17

Bravo AF: 0.0211

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73721294; hg19: chr7-127721934;