17-78168641-G-T

Variant names:

• chr17-78168641-G-T
• rs1456371193
• NM_004710.7:c.25G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004710.7(SYNGR2):​c.25G>T​(p.Ala9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000095 in 1,052,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. A9T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: SYNGR2 NM_004710.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 0 publications found

Genes affected

SYNGR2 (HGNC:11499): (synaptogyrin 2) This gene encodes an integral membrane protein containing four transmembrane regions and a C-terminal cytoplasmic tail that is tyrosine phosphorylated. The exact function of this protein is unclear, but studies of a similar rat protein suggest that it may play a role in regulating membrane traffic in non-neuronal cells. The gene belongs to the synaptogyrin gene family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11089578).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004710.7. 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
	SYNGR2	NM_004710.7	MANE Select	c.25G>T	p.Ala9Ser	missense	Exon 1 of 4	NP_004701.1	O43760-1
	SYNGR2	NM_001363778.1		c.25G>T	p.Ala9Ser	missense	Exon 1 of 3	NP_001350707.1	O43760-2
	SYNGR2	NM_001320523.2		c.25G>T	p.Ala9Ser	missense	Exon 1 of 3	NP_001307452.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR2	ENST00000225777.8	TSL:1 MANE Select	c.25G>T	p.Ala9Ser	missense	Exon 1 of 4	ENSP00000225777.2	O43760-1
	SYNGR2	ENST00000588282.5	TSL:1	c.25G>T	p.Ala9Ser	missense	Exon 1 of 3	ENSP00000467600.1	O43760-2
	SYNGR2	ENST00000585591.5	TSL:5	c.25G>T	p.Ala9Ser	missense	Exon 1 of 5	ENSP00000465678.1	O43760-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.50e-7 AC: 1 AN: 1052990 Hom.: 0 Cov.: 30 AF XY: 0.00000201 AC XY: 1 AN XY: 496974

African (AFR) AF: 0.00 AC: 0 AN: 21836

American (AMR) AF: 0.00 AC: 0 AN: 7452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12930

East Asian (EAS) AF: 0.00 AC: 0 AN: 24016

South Asian (SAS) AF: 0.00 AC: 0 AN: 19320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2756

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 902700

Other (OTH) AF: 0.00 AC: 0 AN: 41508

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.47
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.021
Sift	Benign	0.45	T
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.38		Gain of glycosylation at A9 (P = 0.0095)
MVP		0.067
MPC		0.32
ClinPred		0.091	T
GERP RS		1.7
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.41

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: rs1456371193; hg19: chr17-76164722;