20-24584970-G-C

Variant names:

• chr20-24584970-G-C
• rs370890052
• NM_024893.3:c.595G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024893.3(SYNDIG1):​c.595G>C​(p.Ala199Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A199T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNDIG1 NM_024893.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.66
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

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.595G>C	p.Ala199Pro	missense	Exon 3 of 4	NP_079169.1	Q9H7V2
	SYNDIG1	NM_001323606.2		c.595G>C	p.Ala199Pro	missense	Exon 4 of 5	NP_001310535.1	Q9H7V2
	SYNDIG1	NM_001323607.2		c.595G>C	p.Ala199Pro	missense	Exon 3 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.595G>C	p.Ala199Pro	missense	Exon 3 of 4	ENSP00000366058.3	Q9H7V2
	SYNDIG1	ENST00000892834.1		c.595G>C	p.Ala199Pro	missense	Exon 4 of 5	ENSP00000562893.1
	SYNDIG1	ENST00000892835.1		c.595G>C	p.Ala199Pro	missense	Exon 4 of 5	ENSP00000562894.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	1.6	L
PhyloP100		6.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.60		Loss of helix (P = 0.079)
MVP		0.81
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.83
gMVP		0.92
Mutation Taster		=49/51	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: rs370890052; hg19: chr20-24565606;