chr17-78168630-C-T

Variant names:

• chr17-78168630-C-T
• NM_004710.7:c.14C>T

Variant summary

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

The NM_004710.7(SYNGR2):​c.14C>T​(p.Ala5Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000019 in 1,052,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SYNGR2 NM_004710.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• 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 2 ACMG points.

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

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.14C>T	p.Ala5Val	missense	Exon 1 of 4	NP_004701.1	O43760-1
	SYNGR2	NM_001363778.1		c.14C>T	p.Ala5Val	missense	Exon 1 of 3	NP_001350707.1	O43760-2
	SYNGR2	NM_001320523.2		c.14C>T	p.Ala5Val	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.14C>T	p.Ala5Val	missense	Exon 1 of 4	ENSP00000225777.2	O43760-1
	SYNGR2	ENST00000588282.5	TSL:1	c.14C>T	p.Ala5Val	missense	Exon 1 of 3	ENSP00000467600.1	O43760-2
	SYNGR2	ENST00000585591.5	TSL:5	c.14C>T	p.Ala5Val	missense	Exon 1 of 5	ENSP00000465678.1	O43760-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000190 AC: 2 AN: 1052358 Hom.: 0 Cov.: 30 AF XY: 0.00000201 AC XY: 1 AN XY: 496758

African (AFR) AF: 0.00 AC: 0 AN: 21806

American (AMR) AF: 0.00 AC: 0 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12906

East Asian (EAS) AF: 0.00 AC: 0 AN: 23950

South Asian (SAS) AF: 0.00 AC: 0 AN: 19312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2752

European-Non Finnish (NFE) AF: 0.00000222 AC: 2 AN: 902244

Other (OTH) AF: 0.00 AC: 0 AN: 41472

GnomAD4 genome Cov.: 33

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	0.36
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.79	P
Vest4		0.35
MutPred		0.15		Loss of disorder (P = 0.078)
MVP		0.50
MPC		0.98
ClinPred		0.99	D
GERP RS		3.8
PromoterAI		-0.42	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.75
Mutation Taster		=28/72	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

hg19: chr17-76164711;