7-128081455-T-C

Variant names:

• chr7-128081455-T-C
• rs322825
• NM_014390.4:c.2064T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014390.4(SND1):​c.2064T>C​(p.Thr688Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,613,430 control chromosomes in the GnomAD database, including 350,634 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 0.72 (40578 hom., cov: 34)
  • Exomes 𝑓: 0.65 (310056 hom.)
• Consequence: SND1 NM_014390.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91
• Publications: 34 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SND1	NM_014390.4	MANE Select	c.2064T>C	p.Thr688Thr	synonymous	Exon 18 of 24	NP_055205.2	Q7KZF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SND1	ENST00000354725.8	TSL:1 MANE Select	c.2064T>C	p.Thr688Thr	synonymous	Exon 18 of 24	ENSP00000346762.3	Q7KZF4
	SND1	ENST00000903603.1		c.2247T>C	p.Thr749Thr	synonymous	Exon 19 of 25	ENSP00000573662.1
	SND1	ENST00000915268.1		c.2154T>C	p.Thr718Thr	synonymous	Exon 19 of 25	ENSP00000585327.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108980 AN: 152066 Hom.: 40528 Cov.: 34

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.713

GnomAD2 exomes AF: 0.640 AC: 160627 AN: 250918 AF XY: 0.633

Gnomad AFR exome AF: 0.923

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.330

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.652

Gnomad OTH exome AF: 0.662

GnomAD4 exome AF: 0.646 AC: 944068 AN: 1461246 Hom.: 310056 Cov.: 51 AF XY: 0.642 AC XY: 466959 AN XY: 726944

African (AFR) AF: 0.927 AC: 31020 AN: 33478

American (AMR) AF: 0.685 AC: 30634 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 20360 AN: 26134

East Asian (EAS) AF: 0.291 AC: 11545 AN: 39674

South Asian (SAS) AF: 0.586 AC: 50567 AN: 86250

European-Finnish (FIN) AF: 0.578 AC: 30816 AN: 53358

Middle Eastern (MID) AF: 0.733 AC: 4224 AN: 5766

European-Non Finnish (NFE) AF: 0.652 AC: 725029 AN: 1111514

Other (OTH) AF: 0.661 AC: 39873 AN: 60366

GnomAD4 genome AF: 0.717 AC: 109086 AN: 152184 Hom.: 40578 Cov.: 34 AF XY: 0.708 AC XY: 52663 AN XY: 74406

African (AFR) AF: 0.915 AC: 38033 AN: 41560

American (AMR) AF: 0.710 AC: 10861 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2751 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1672 AN: 5148

South Asian (SAS) AF: 0.598 AC: 2885 AN: 4822

European-Finnish (FIN) AF: 0.577 AC: 6110 AN: 10586

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44388 AN: 67988

Other (OTH) AF: 0.712 AC: 1503 AN: 2110

Alfa AF: 0.684 Hom.: 53826

Bravo AF: 0.736

Asia WGS AF: 0.521 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.53
PhyloP100		-4.9
Mutation Taster		=98/2	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: rs322825; hg19: chr7-127721507; COSMIC: COSV61246161; COSMIC: COSV61246161;