20-24543122-A-G

Variant names:

• chr20-24543122-A-G
• NM_024893.3:c.25A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024893.3(SYNDIG1):​c.25A>G​(p.Ser9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNDIG1 NM_024893.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.572
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046772897).

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.25A>G	p.Ser9Gly	missense	Exon 2 of 4	NP_079169.1	Q9H7V2
	SYNDIG1	NM_001323606.2		c.25A>G	p.Ser9Gly	missense	Exon 3 of 5	NP_001310535.1	Q9H7V2
	SYNDIG1	NM_001323607.2		c.25A>G	p.Ser9Gly	missense	Exon 2 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.25A>G	p.Ser9Gly	missense	Exon 2 of 4	ENSP00000366058.3	Q9H7V2
	SYNDIG1	ENST00000892834.1		c.25A>G	p.Ser9Gly	missense	Exon 3 of 5	ENSP00000562893.1
	SYNDIG1	ENST00000892835.1		c.25A>G	p.Ser9Gly	missense	Exon 3 of 5	ENSP00000562894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Benign	0.065
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.98	L
PhyloP100		0.57
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.33
MPC		0.24
ClinPred		0.097	T
GERP RS		0.97
Varity_R		0.043
gMVP		0.19
Mutation Taster		=97/3	polymorphism

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

hg19: chr20-24523758;