16-1992038-C-T

Variant names:

• chr16-1992038-C-T
• rs755280789
• NM_004209.6:c.164C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004209.6(SYNGR3):​c.164C>T​(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P55R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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]

ENSG00000299741 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34529597).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004209.6. 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
	SYNGR3	NM_004209.6	MANE Select	c.164C>T	p.Pro55Leu	missense	Exon 2 of 4	NP_004200.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR3	ENST00000248121.7	TSL:1 MANE Select	c.164C>T	p.Pro55Leu	missense	Exon 2 of 4	ENSP00000248121.2	O43761
	SYNGR3	ENST00000873156.1		c.164C>T	p.Pro55Leu	missense	Exon 2 of 4	ENSP00000543215.1
	SYNGR3	ENST00000568896.1	TSL:5	c.284C>T	p.Pro95Leu	missense	Exon 3 of 4	ENSP00000454756.1	H3BNA6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428584 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 708010

African (AFR) AF: 0.00 AC: 0 AN: 31986

American (AMR) AF: 0.00 AC: 0 AN: 40540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25442

East Asian (EAS) AF: 0.00 AC: 0 AN: 37550

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4628

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097550

Other (OTH) AF: 0.00 AC: 0 AN: 59002

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.20
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.27		Loss of disorder (P = 0.0588)
MVP		0.71
MPC		0.94
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.23
gMVP		0.36

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

dbSNP: rs755280789; hg19: chr16-2042039;