chr16-1992038-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGR3	NM_004209.6	c.164C>T	p.Pro55Leu	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.164C>T	p.Pro55Leu	missense_variant	Exon 2 of 4	1	NM_004209.6	ENSP00000248121.2
SYNGR3	ENST00000568896.1	c.284C>T	p.Pro95Leu	missense_variant	Exon 3 of 4	5		ENSP00000454756.1
SYNGR3	ENST00000563869.1	c.96C>T	p.Pro32Pro	synonymous_variant	Exon 2 of 4	2		ENSP00000455344.1
SYNGR3	ENST00000562045	c.-102C>T		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000455577.1

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

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: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.9	D;.;D
REVEL	Benign	0.20
Sift	Benign	0.19	T;.;D
Sift4G	Benign	0.17	T;D;T
Polyphen		1.0	D;.;.
Vest4		0.45
MutPred		0.27		Loss of disorder (P = 0.0588);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2042039;