Genetic Variant GJC1:c.*325_*326delTT (chr17-44804300-TAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005497.4(GJC1):c.*325_*326delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 188,308 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0024 ( 0 hom. )

Consequence

GJC1
NM_005497.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.05

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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_326delTT		3_prime_UTR	Exon 3 of 3	NP_005488.2	P36383
	GJC1	NM_001080383.2		c.325_326delTT		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_326delTT	3_prime_UTR	Exon 3 of 3	ENSP00000467201.1	P36383
GJC1	ENST00000330514.4	TSL:2	c.325_326delTT	3_prime_UTR	Exon 2 of 2	ENSP00000333193.3	P36383
GJC1	ENST00000590758.3	TSL:3	c.325_326delTT	3_prime_UTR	Exon 2 of 2	ENSP00000466339.1	P36383

Frequencies

GnomAD3 genomes

AF:

0.00000693

AC:

AN:

144364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00241

AC:

106

AN:

43944

Hom.:

AF XY:

0.00221

AC XY:

AN XY:

22188

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

1422

American (AMR)

AF:

0.00295

AC:

AN:

2370

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

1606

East Asian (EAS)

AF:

0.00236

AC:

AN:

2544

South Asian (SAS)

AF:

0.00187

AC:

AN:

1070

European-Finnish (FIN)

AF:

0.000867

AC:

AN:

2306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.00275

AC:

AN:

29472

Other (OTH)

AF:

0.00202

AC:

AN:

2968

⚠️ 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: 0.235

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:

0.00000693

AC:

AN:

144364

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69974

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

39636

American (AMR)

AF:

0.00

AC:

AN:

14394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5020

South Asian (SAS)

AF:

0.00

AC:

AN:

4552

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

8888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65352

Other (OTH)

AF:

0.00

AC:

AN:

1956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-44804300-TAAAAAA-TAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over