NM_030772.5:c.1348G>T

Variant names:

• chr1-38874751-C-A
• rs148366607
• NM_030772.5:c.1348G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030772.5(GJA9):​c.1348G>T​(p.Gly450Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. G450S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJA9 NM_030772.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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]

ENSG00000274944 (HGNC:):

RRAGC-DT (HGNC:55793): (RRAGC divergent transcript)

ACMG classification

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=0.070227206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJA9	NM_030772.5	c.1348G>T	p.Gly450Cys	missense_variant	Exon 2 of 2	ENST00000357771.5	NP_110399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA9	ENST00000357771.5	c.1348G>T	p.Gly450Cys	missense_variant	Exon 2 of 2	1	NM_030772.5	ENSP00000350415.3
ENSG00000274944	ENST00000621281.1	c.37-1661G>T		intron_variant	Intron 1 of 4	2		ENSP00000479064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	.;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.070	T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.050	T;T
Polyphen		0.019	B;B
Vest4		0.13
MutPred		0.35		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.15
MPC		0.25
ClinPred		0.68	D
GERP RS		-0.015
Varity_R		0.23
gMVP		0.18

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

Other links and lift over

dbSNP: rs148366607; hg19: chr1-39340423;