rs11087473

Variant names:

• chr20-24649158-G-A
• rs11087473
• NM_024893.3:c.619-16188G>A

Variant summary

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

The NM_024893.3(SYNDIG1):​c.619-16188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,166 control chromosomes in the GnomAD database, including 3,569 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 0.20 (3569 hom., cov: 32)
• Consequence: SYNDIG1 NM_024893.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 2 publications found

Genes affected

SYNDIG1 (HGNC:15885): (synapse differentiation inducing 1) This gene encodes a protein that belongs to the interferon-induced transmembrane family of proteins. A similar protein in rat is thought to regulate the development of excitatory synapses. [provided by RefSeq, Jul 2013]

SYNDIG1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024893.3. 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
	SYNDIG1	NM_024893.3	MANE Select	c.619-16188G>A		intron	N/A	NP_079169.1
	SYNDIG1	NM_001323606.2		c.619-16188G>A		intron	N/A	NP_001310535.1
	SYNDIG1	NM_001323607.2		c.619-16188G>A		intron	N/A	NP_001310536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNDIG1	ENST00000376862.4	TSL:1 MANE Select	c.619-16188G>A		intron	N/A	ENSP00000366058.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29683 AN: 152048 Hom.: 3567 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29687 AN: 152166 Hom.: 3569 Cov.: 32 AF XY: 0.197 AC XY: 14620 AN XY: 74372

African (AFR) AF: 0.0675 AC: 2805 AN: 41536

American (AMR) AF: 0.192 AC: 2938 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2375 AN: 5156

South Asian (SAS) AF: 0.197 AC: 952 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10578

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16208 AN: 67988

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.187 Hom.: 538

Bravo AF: 0.192

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.58
PhyloP100		-0.46
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: rs11087473; hg19: chr20-24629794;