20-24665467-C-T

Variant names:

• chr20-24665467-C-T
• rs1277162790
• NM_024893.3:c.740C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024893.3(SYNDIG1):​c.740C>T​(p.Ala247Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SYNDIG1 NM_024893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNDIG1	NM_024893.3	MANE Select	c.740C>T	p.Ala247Val	missense	Exon 4 of 4	NP_079169.1	Q9H7V2
	SYNDIG1	NM_001323606.2		c.740C>T	p.Ala247Val	missense	Exon 5 of 5	NP_001310535.1	Q9H7V2
	SYNDIG1	NM_001323607.2		c.740C>T	p.Ala247Val	missense	Exon 4 of 4	NP_001310536.1	Q9H7V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNDIG1	ENST00000376862.4	TSL:1 MANE Select	c.740C>T	p.Ala247Val	missense	Exon 4 of 4	ENSP00000366058.3	Q9H7V2
	SYNDIG1	ENST00000892834.1		c.740C>T	p.Ala247Val	missense	Exon 5 of 5	ENSP00000562893.1
	SYNDIG1	ENST00000892835.1		c.740C>T	p.Ala247Val	missense	Exon 5 of 5	ENSP00000562894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251136 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461718 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.048	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	0.97	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.72	N
REVEL	Uncertain	0.46
Sift	Benign	0.032	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.24		Gain of sheet (P = 0.0477)
MVP		0.83
MPC		0.73
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.24
gMVP		0.91
Mutation Taster		=20/80	disease causing

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: rs1277162790; hg19: chr20-24646103; COSMIC: COSV106535569;