chr1-109603476-C-T

Variant summary

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

The NM_001377295.2(GNAT2):​c.943G>A​(p.Asp315Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,454,738 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 (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GNAT2
NM_001377295.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.82
Variant links:
Genes affected
GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.31333715).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GNAT2NM_001377295.2 linkuse as main transcriptc.943G>A p.Asp315Asn missense_variant 9/9 ENST00000679935.1
GNAT2NM_001379232.1 linkuse as main transcriptc.943G>A p.Asp315Asn missense_variant 9/9
GNAT2NM_005272.5 linkuse as main transcriptc.943G>A p.Asp315Asn missense_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GNAT2ENST00000679935.1 linkuse as main transcriptc.943G>A p.Asp315Asn missense_variant 9/9 NM_001377295.2 P1
GNAT2ENST00000351050.8 linkuse as main transcriptc.943G>A p.Asp315Asn missense_variant 8/81 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1454738
Hom.:
0
Cov.:
28
AF XY:
0.00000552
AC XY:
4
AN XY:
724192
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:
0.00
Gnomad4 NFE exome
AF:
0.00000543
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Achromatopsia 4 Uncertain:1
Uncertain significance, no assertion criteria providedresearchMolecular Genetics Laboratory, Institute for Ophthalmic ResearchJun 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.29
T
MutationAssessor
Benign
0.86
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.39
Sift
Benign
0.060
T
Sift4G
Benign
0.14
T
Polyphen
0.089
B
Vest4
0.34
MutPred
0.42
Loss of ubiquitination at K314 (P = 0.046);
MVP
0.89
MPC
0.31
ClinPred
0.95
D
GERP RS
5.5
Varity_R
0.31
gMVP
0.61

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: rs950519744; hg19: chr1-110146098; API