1-38874559-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030772.5(GJA9):ā€‹c.1540C>Gā€‹(p.Gln514Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,610,904 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000023 ( 0 hom. )

Consequence

GJA9
NM_030772.5 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
Variant links:
Genes affected
GJA9 (HGNC:19155): (gap junction protein alpha 9) Connexins, such as GJA9, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]
RRAGC-DT (HGNC:55793): (RRAGC divergent transcript)

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=0.123042375).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GJA9NM_030772.5 linkc.1540C>G p.Gln514Glu missense_variant 2/2 ENST00000357771.5 NP_110399.2 P57773-1A0A654IBV8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GJA9ENST00000357771.5 linkc.1540C>G p.Gln514Glu missense_variant 2/21 NM_030772.5 ENSP00000350415.3 P57773-1
ENSG00000274944ENST00000621281.1 linkc.37-1469C>G intron_variant 2 ENSP00000479064.1 A0A087WV05

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000598
AC:
15
AN:
250868
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135580
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1458726
Hom.:
0
Cov.:
29
AF XY:
0.0000289
AC XY:
21
AN XY:
725844
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:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsFeb 28, 2024The c.1540C>G (p.Q514E) alteration is located in exon 2 (coding exon 1) of the GJA9 gene. This alteration results from a C to G substitution at nucleotide position 1540, causing the glutamine (Q) at amino acid position 514 to be replaced by a glutamic acid (E). 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
Benign
0.11
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Uncertain
0.050
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.068
T;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.44
.;T
M_CAP
Uncertain
0.088
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Uncertain
0.42
D
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.90
N;N
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.067
B;B
Vest4
0.37
MVP
0.22
MPC
0.38
ClinPred
0.34
T
GERP RS
2.2
Varity_R
0.43
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: rs140099991; hg19: chr1-39340231; API