10-127137863-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001039762.3(INSYN2A):c.1414G>A(p.Gly472Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
INSYN2A
NM_001039762.3 missense
NM_001039762.3 missense
Scores
2
6
6
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
INSYN2A (HGNC:33859): (inhibitory synaptic factor 2A) Predicted to be involved in inhibitory postsynaptic potential. Predicted to be active in postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]
DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21569604).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSYN2A | NM_001039762.3 | c.1414G>A | p.Gly472Arg | missense_variant | 6/6 | ENST00000522781.6 | |
DOCK1 | NM_001290223.2 | c.2847+10099C>T | intron_variant | ENST00000623213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSYN2A | ENST00000522781.6 | c.1414G>A | p.Gly472Arg | missense_variant | 6/6 | 2 | NM_001039762.3 | P1 | |
DOCK1 | ENST00000623213.2 | c.2847+10099C>T | intron_variant | 1 | NM_001290223.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250970Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135626
GnomAD3 exomes
AF:
AC:
4
AN:
250970
Hom.:
AF XY:
AC XY:
2
AN XY:
135626
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727156
GnomAD4 exome
AF:
AC:
21
AN:
1461706
Hom.:
Cov.:
31
AF XY:
AC XY:
11
AN XY:
727156
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74350
GnomAD4 genome
?
AF:
AC:
5
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74350
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1414G>A (p.G472R) alteration is located in exon 6 (coding exon 3) of the FAM196A gene. This alteration results from a G to A substitution at nucleotide position 1414, causing the glycine (G) at amino acid position 472 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
Sift4G
Uncertain
D;T;D
Polyphen
1.0
.;D;.
Vest4
MutPred
0.21
.;Loss of sheet (P = 0.0126);.;
MVP
MPC
0.63
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at