dbSNP rs755280789: SYNGR3:p.Pro55His (chr16-1992038-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004209.6(SYNGR3):c.164C>A(p.Pro55His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 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: 7.0e-7 ( 0 hom. )

Consequence

SYNGR3
NM_004209.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Variant links:

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]

SYNGR3 links:

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ACMG classification

Classification made for transcript

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=0.32506233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGR3	NM_004209.6 link	c.164C>A	p.Pro55His	missense_variant	Exon 2 of 4	ENST00000248121.7	NP_004200.2	O43761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNGR3	ENST00000248121.7 link	c.164C>A	p.Pro55His	missense_variant	Exon 2 of 4	1	NM_004209.6	ENSP00000248121.2	O43761
SYNGR3	ENST00000568896.1 link	c.284C>A	p.Pro95His	missense_variant	Exon 3 of 4	5		ENSP00000454756.1	H3BNA6
SYNGR3	ENST00000563869.1 link	c.96C>A	p.Pro32Pro	synonymous_variant	Exon 2 of 4	2		ENSP00000455344.1	H3BPJ5
SYNGR3	ENST00000562045 link	c.-102C>A		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000455577.1	H3BQ28

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000534

AC:

AN:

187246

Hom.:

AF XY:

0.00

AC XY:

AN XY:

103726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000602

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708010

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.41

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.9

D;.;D

REVEL

Benign

0.18

Sift

Benign

0.075

T;.;D

Sift4G

Benign

0.069

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.51

MutPred

0.25

Gain of catalytic residue at P55 (P = 0.0804);Gain of catalytic residue at P55 (P = 0.0804);.;

MVP

0.65

MPC

1.6

ClinPred

0.96

GERP RS

4.3

Varity_R

0.27

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over