chr1-38874709-A-G

Variant names:

• chr1-38874709-A-G
• rs61745441
• NM_030772.5:c.1390T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_030772.5(GJA9):​c.1390T>C​(p.Ser464Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,614,154 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (55 hom.)
• Consequence: GJA9 NM_030772.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.369
• Publications: 12 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026267767).
• BP6: Variant 1-38874709-A-G is Benign according to our data. Variant chr1-38874709-A-G is described in ClinVar as Benign. ClinVar VariationId is 772681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.1390T>C	p.Ser464Pro	missense	Exon 2 of 2	NP_110399.2
	GJA9-MYCBP	NR_037633.1		n.1680T>C		non_coding_transcript_exon	Exon 2 of 6
	GJA9-MYCBP	NR_037634.1		n.1611+69T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA9	ENST00000357771.5	TSL:1 MANE Select	c.1390T>C	p.Ser464Pro	missense	Exon 2 of 2	ENSP00000350415.3	P57773-1
	ENSG00000274944	ENST00000621281.1	TSL:2	c.37-1619T>C		intron	N/A	ENSP00000479064.1	A0A087WV05
	GJA9	ENST00000360786.3	TSL:6	c.1390T>C	p.Ser464Pro	missense	Exon 1 of 1	ENSP00000354020.3	P57773-1

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 792 AN: 152148 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00656

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00676 AC: 1700 AN: 251488 AF XY: 0.00708

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00361

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.00723

Gnomad OTH exome AF: 0.00993

GnomAD4 exome AF: 0.00724 AC: 10585 AN: 1461888 Hom.: 55 Cov.: 35 AF XY: 0.00729 AC XY: 5301 AN XY: 727246

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.00425 AC: 190 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00624 AC: 163 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00820 AC: 707 AN: 86258

European-Finnish (FIN) AF: 0.0162 AC: 863 AN: 53418

Middle Eastern (MID) AF: 0.0172 AC: 99 AN: 5768

European-Non Finnish (NFE) AF: 0.00729 AC: 8106 AN: 1112008

Other (OTH) AF: 0.00695 AC: 420 AN: 60396

GnomAD4 genome AF: 0.00519 AC: 791 AN: 152266 Hom.: 2 Cov.: 32 AF XY: 0.00552 AC XY: 411 AN XY: 74432

African (AFR) AF: 0.00142 AC: 59 AN: 41560

American (AMR) AF: 0.00321 AC: 49 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00621 AC: 30 AN: 4830

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68010

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00664 Hom.: 4

Bravo AF: 0.00459

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00640 AC: 55

ExAC AF: 0.00696 AC: 845

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.00676

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.1
DANN	Benign	0.87
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0026	T
MetaSVM	Uncertain	0.042	D
MutationAssessor	Benign	-1.2	N
PhyloP100		0.37
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.23
Sift	Benign	0.57	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.021
MVP		0.092
MPC		0.088
ClinPred		0.00031	T
GERP RS		2.0
Varity_R		0.072
gMVP		0.085
Mutation Taster		=100/0	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: rs61745441; hg19: chr1-39340381; COSMIC: COSV62532023; COSMIC: COSV62532023;