NM_004710.7:c.578C>A

Variant names:

• chr17-78171839-C-A
• NM_004710.7:c.578C>A

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.578C>A​(p.Ala193Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: SYNGR2 NM_004710.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• 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=0.2251397).

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.578C>A	p.Ala193Asp	missense	Exon 4 of 4	NP_004701.1	O43760-1
	SYNGR2	NM_001363778.1		c.667C>A	p.Pro223Thr	missense	Exon 3 of 3	NP_001350707.1	O43760-2
	SYNGR2	NM_001320523.2		c.*30C>A		3_prime_UTR	Exon 3 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.578C>A	p.Ala193Asp	missense	Exon 4 of 4	ENSP00000225777.2	O43760-1
	SYNGR2	ENST00000588282.5	TSL:1	c.667C>A	p.Pro223Thr	missense	Exon 3 of 3	ENSP00000467600.1	O43760-2
	SYNGR2	ENST00000585591.5	TSL:5	c.578C>A	p.Ala193Asp	missense	Exon 4 of 5	ENSP00000465678.1	O43760-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.27
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.038	D
Polyphen		0.18	B
Vest4		0.36
MutPred		0.21		Gain of phosphorylation at Y195 (P = 0.0765)
MVP		0.59
MPC		0.52
ClinPred		0.58	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-76167920;