16-1992134-T-C

Variant names:

• chr16-1992134-T-C
• NM_004209.6:c.260T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004209.6(SYNGR3):​c.260T>C​(p.Leu87Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

Genes affected

SYNGR3 (HGNC:11501): (synaptogyrin 3) This gene encodes an integral membrane protein. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it is a synaptic vesicle protein that also interacts with the dopamine transporter. The gene product belongs to the synaptogyrin gene family. [provided by RefSeq, Dec 2010]

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
SYNGR3	NM_004209.6	c.260T>C	p.Leu87Pro	missense_variant	Exon 2 of 4	ENST00000248121.7	NP_004200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNGR3	ENST00000248121.7	c.260T>C	p.Leu87Pro	missense_variant	Exon 2 of 4	1	NM_004209.6	ENSP00000248121.2
SYNGR3	ENST00000568896.1	c.380T>C	p.Leu127Pro	missense_variant	Exon 3 of 4	5		ENSP00000454756.1
SYNGR3	ENST00000563869.1	c.192T>C	p.Ala64Ala	synonymous_variant	Exon 2 of 4	2		ENSP00000455344.1
SYNGR3	ENST00000562045	c.-6T>C		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000455577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384964 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683038

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260T>C (p.L87P) alteration is located in exon 2 (coding exon 2) of the SYNGR3 gene. This alteration results from a T to C substitution at nucleotide position 260, causing the leucine (L) at amino acid position 87 to be replaced by a proline (P). 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	0.41
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;T;T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.5	D;.;D
REVEL	Benign	0.29
Sift	Uncertain	0.016	D;.;D
Sift4G	Benign	0.087	T;D;D
Polyphen		0.99	D;.;.
Vest4		0.83
MutPred		0.64		Loss of stability (P = 0.0072);Loss of stability (P = 0.0072);.;
MVP		0.35
MPC		1.9
ClinPred		0.91	D
GERP RS		4.2
Varity_R		0.89
gMVP		0.89

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: chr16-2042135;