chr17-44804300-TAA-T

Variant names:

• chr17-44804300-TAA-T
• rs199789186
• NM_005497.4:c.*325_*326delTT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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: 1 AN: 144364 Hom.: 0 Cov.: 29

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.: 0 AF XY: 0.00221 AC XY: 49 AN XY: 22188

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

African (AFR) AF: 0.00 AC: 0 AN: 1422

American (AMR) AF: 0.00295 AC: 7 AN: 2370

Ashkenazi Jewish (ASJ) AF: 0.00125 AC: 2 AN: 1606

East Asian (EAS) AF: 0.00236 AC: 6 AN: 2544

South Asian (SAS) AF: 0.00187 AC: 2 AN: 1070

European-Finnish (FIN) AF: 0.000867 AC: 2 AN: 2306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.00275 AC: 81 AN: 29472

Other (OTH) AF: 0.00202 AC: 6 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.

GnomAD4 genome AF: 0.00000693 AC: 1 AN: 144364 Hom.: 0 Cov.: 29 AF XY: 0.0000143 AC XY: 1 AN XY: 69974

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

African (AFR) AF: 0.00 AC: 0 AN: 39636

American (AMR) AF: 0.00 AC: 0 AN: 14394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5020

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.000113 AC: 1 AN: 8888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65352

Other (OTH) AF: 0.00 AC: 0 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.

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

Other links and lift over

dbSNP: rs199789186; hg19: chr17-42881668;