NM_007247.6:c.3332G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007247.6(SYNRG):​c.3332G>C​(p.Arg1111Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SYNRG
NM_007247.6 missense

Scores

7
4
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88
Variant links:
Genes affected
SYNRG (HGNC:557): (synergin gamma) This gene encodes a protein that interacts with the gamma subunit of AP1 clathrin-adaptor complex. The AP1 complex is located at the trans-Golgi network and associates specific proteins with clathrin-coated vesicles. This encoded protein may act to connect the AP1 complex to other proteins. Alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNRGNM_007247.6 linkc.3332G>C p.Arg1111Pro missense_variant Exon 16 of 22 ENST00000612223.5 NP_009178.3 Q9UMZ2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNRGENST00000612223.5 linkc.3332G>C p.Arg1111Pro missense_variant Exon 16 of 22 1 NM_007247.6 ENSP00000483453.1 Q9UMZ2-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251262
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135794
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:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3332G>C (p.R1111P) alteration is located in exon 16 (coding exon 16) of the SYNRG gene. This alteration results from a G to C substitution at nucleotide position 3332, causing the arginine (R) at amino acid position 1111 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.;.;.;.;.;T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;.;.;.;.;.;D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.64
D;D;D;D;D;D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.7
L;.;.;.;.;.;.
PrimateAI
Pathogenic
0.89
D
Sift4G
Uncertain
0.010
D;D;D;D;D;D;.
Polyphen
1.0
D;D;.;.;.;.;.
Vest4
0.90
MutPred
0.34
Loss of helix (P = 0.0167);.;.;.;.;.;.;
MVP
0.30
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.64
gMVP
0.57

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.

Other links and lift over

dbSNP: rs773316300; hg19: chr17-35900516; API