chr16-1992154-C-A

Variant names:

• chr16-1992154-C-A
• NM_004209.6:c.280C>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.280C>A​(p.Gln94Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. Q94H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• 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=0.4027878).

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.280C>A	p.Gln94Lys	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.280C>A	p.Gln94Lys	missense	Exon 2 of 4	ENSP00000248121.2	O43761
	SYNGR3	ENST00000563869.1	TSL:2	c.212C>A	p.Ala71Glu	missense	Exon 2 of 4	ENSP00000455344.1	H3BPJ5
	SYNGR3	ENST00000873156.1		c.280C>A	p.Gln94Lys	missense	Exon 2 of 4	ENSP00000543215.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.36e-7 AC: 1 AN: 1358894 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 667916

⚠️ 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: 28070

American (AMR) AF: 0.00 AC: 0 AN: 32832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23728

East Asian (EAS) AF: 0.00 AC: 0 AN: 32636

South Asian (SAS) AF: 0.00 AC: 0 AN: 76936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4326

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061940

Other (OTH) AF: 0.00 AC: 0 AN: 56052

⚠️ 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

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	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.40	T
PhyloP100		3.7
PROVEAN	Pathogenic	-5.0	D
Sift4G	Pathogenic	0.0	D
MVP		0.32
ClinPred		0.96	D
GERP RS		3.2
Varity_R		0.62

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: chr16-2042155;