17-78168630-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGR2	NM_004710.7	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 4	ENST00000225777.8	NP_004701.1
SYNGR2	NM_001363778.1	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 3		NP_001350707.1
SYNGR2	NM_001320523.2	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 3		NP_001307452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNGR2	ENST00000225777.8	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 4	1	NM_004710.7	ENSP00000225777.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000222

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14C>T (p.A5V) alteration is located in exon 1 (coding exon 1) of the SYNGR2 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D;T;D
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.3	M;M;.;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	D;.;.;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D;.;.;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.79	P;P;.;.
Vest4		0.35
MutPred		0.15		Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);
MVP		0.50
MPC		0.98
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-76164711;