Genetic Variant GJC1:c.*325_*326dupTT (chr17-44804300-T-TAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005497.4(GJC1):c.*325_*326dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 188,524 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0041 ( 0 hom. )

Consequence

GJC1
NM_005497.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.963

Publications

0 publications found

Variant links:

Genes affected

GJC1 (HGNC:4280): (gap junction protein gamma 1) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

GJC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 208 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005497.4. 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
	GJC1	NM_005497.4	MANE Select	c.325_326dupTT		3_prime_UTR	Exon 3 of 3	NP_005488.2	P36383
	GJC1	NM_001080383.2		c.325_326dupTT		3_prime_UTR	Exon 3 of 3	NP_001073852.1	P36383

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJC1	ENST00000592524.6	TSL:2 MANE Select	c.325_326dupTT	3_prime_UTR	Exon 3 of 3	ENSP00000467201.1	P36383
GJC1	ENST00000330514.4	TSL:2	c.325_326dupTT	3_prime_UTR	Exon 2 of 2	ENSP00000333193.3	P36383
GJC1	ENST00000590758.3	TSL:3	c.325_326dupTT	3_prime_UTR	Exon 2 of 2	ENSP00000466339.1	P36383

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

208

AN:

144368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000689

Gnomad OTH

AF:

0.000511

GnomAD4 exome

AF:

0.00413

AC:

182

AN:

44094

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

AN XY:

22266

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00846

AC:

AN:

1418

American (AMR)

AF:

0.00168

AC:

AN:

2380

Ashkenazi Jewish (ASJ)

AF:

0.00435

AC:

AN:

1608

East Asian (EAS)

AF:

0.00352

AC:

AN:

2556

South Asian (SAS)

AF:

0.00741

AC:

AN:

1080

European-Finnish (FIN)

AF:

0.0104

AC:

AN:

2312

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.00362

AC:

107

AN:

29582

Other (OTH)

AF:

0.00269

AC:

AN:

2972

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.295

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00144

AC:

208

AN:

144430

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

137

AN XY:

70052

show subpopulations

African (AFR)

AF:

0.0000503

AC:

AN:

39722

American (AMR)

AF:

0.000139

AC:

AN:

14414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5008

South Asian (SAS)

AF:

0.00

AC:

AN:

4540

European-Finnish (FIN)

AF:

0.0178

AC:

158

AN:

8886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.000689

AC:

AN:

65344

Other (OTH)

AF:

0.000507

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00212

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.96

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over