rs1001739073

Variant names:

• chr16-1992121-G-A
• rs1001739073
• NM_004209.6:c.247G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-1992121-G-A
• chr16-1992121-G-C
• chr16-1992121-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004209.6(SYNGR3):​c.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. A83S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22308502).

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.247G>A	p.Ala83Thr	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.247G>A	p.Ala83Thr	missense	Exon 2 of 4	ENSP00000248121.2	O43761
	SYNGR3	ENST00000563869.1	TSL:2	c.179G>A	p.Arg60His	missense	Exon 2 of 4	ENSP00000455344.1	H3BPJ5
	SYNGR3	ENST00000873156.1		c.247G>A	p.Ala83Thr	missense	Exon 2 of 4	ENSP00000543215.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398420 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690972

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29674

American (AMR) AF: 0.00 AC: 0 AN: 37496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24736

East Asian (EAS) AF: 0.00 AC: 0 AN: 35108

South Asian (SAS) AF: 0.00 AC: 0 AN: 80598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4650

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082616

Other (OTH) AF: 0.00 AC: 0 AN: 57588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.86
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.036
Sift	Benign	0.089	T
Sift4G	Benign	0.19	T
Polyphen		0.68	P
Vest4		0.30
MutPred		0.39		Gain of sheet (P = 0.0827)
MVP		0.16
MPC		0.69
ClinPred		0.30	T
GERP RS		1.0
Varity_R		0.11
gMVP		0.28

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

dbSNP: rs1001739073; hg19: chr16-2042122;