1-38875237-C-A

Variant names:

• chr1-38875237-C-A
• rs768572976
• NM_030772.5:c.862G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030772.5(GJA9):​c.862G>T​(p.Val288Leu) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJA9 NM_030772.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059283733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030772.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA9	NM_030772.5	MANE Select	c.862G>T	p.Val288Leu	missense	Exon 2 of 2	NP_110399.2
	GJA9-MYCBP	NR_037633.1		n.1152G>T		non_coding_transcript_exon	Exon 2 of 6
	GJA9-MYCBP	NR_037634.1		n.1152G>T		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA9	ENST00000357771.5	TSL:1 MANE Select	c.862G>T	p.Val288Leu	missense	Exon 2 of 2	ENSP00000350415.3	P57773-1
	ENSG00000274944	ENST00000621281.1	TSL:2	c.37-2147G>T		intron	N/A	ENSP00000479064.1	A0A087WV05
	GJA9	ENST00000360786.3	TSL:6	c.862G>T	p.Val288Leu	missense	Exon 1 of 1	ENSP00000354020.3	P57773-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251026 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	6.6
DANN	Benign	0.91
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.059	T
MetaSVM	Uncertain	0.091	D
MutationAssessor	Benign	1.4	L
PhyloP100		0.21
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.23
Sift	Benign	0.47	T
Sift4G	Benign	0.60	T
Polyphen		0.010	B
Vest4		0.099
MutPred		0.22		Loss of methylation at K290 (P = 0.0653)
MVP		0.56
MPC		0.071
ClinPred		0.035	T
GERP RS		2.0
Varity_R		0.051
gMVP		0.22
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs768572976; hg19: chr1-39340909;