16-1990158-G-A

Variant names:

• chr16-1990158-G-A
• NM_004209.6:c.56G>A

Variant summary

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

The NM_004209.6(SYNGR3):​c.56G>A​(p.Ser19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000027 in 1,110,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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]

ENSG00000261790 (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=0.32942075).

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.56G>A	p.Ser19Asn	missense	Exon 1 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.56G>A	p.Ser19Asn	missense	Exon 1 of 4	ENSP00000248121.2	O43761
	SYNGR3	ENST00000873156.1		c.56G>A	p.Ser19Asn	missense	Exon 1 of 4	ENSP00000543215.1
	SYNGR3	ENST00000568896.1	TSL:5	c.2G>A	p.Ser1Asn	missense	Exon 1 of 4	ENSP00000454756.1	H3BNA6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000270 AC: 3 AN: 1110190 Hom.: 0 Cov.: 30 AF XY: 0.00000189 AC XY: 1 AN XY: 529648

African (AFR) AF: 0.00 AC: 0 AN: 23030

American (AMR) AF: 0.00 AC: 0 AN: 10066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15350

East Asian (EAS) AF: 0.00 AC: 0 AN: 26328

South Asian (SAS) AF: 0.00 AC: 0 AN: 30474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3064

European-Non Finnish (NFE) AF: 0.00000321 AC: 3 AN: 933696

Other (OTH) AF: 0.00 AC: 0 AN: 44650

GnomAD4 genome Cov.: 31

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	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.061
Sift	Benign	0.45	T
Sift4G	Benign	0.49	T
Polyphen		0.039	B
Vest4		0.19
MutPred		0.20		Gain of MoRF binding (P = 0.1317)
MVP		0.43
MPC		0.60
ClinPred		0.069	T
GERP RS		3.3
PromoterAI		-0.036	Neutral
Varity_R		0.11
gMVP		0.25

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: chr16-2040159;