17-44804300-TAAAAAA-TAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJC1	NM_005497.4	c.*325_*326dupTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000592524.6	NP_005488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJC1	ENST00000592524	c.*325_*326dupTT		3_prime_UTR_variant	Exon 3 of 3	2	NM_005497.4	ENSP00000467201.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 208 AN: 144368 Hom.: 1 Cov.: 29

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.: 0 Cov.: 0 AF XY: 0.00422 AC XY: 94 AN XY: 22266

Gnomad4 AFR exome AF: 0.00846

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00435

Gnomad4 EAS exome AF: 0.00352

Gnomad4 SAS exome AF: 0.00741

Gnomad4 FIN exome AF: 0.0104

Gnomad4 NFE exome AF: 0.00362

Gnomad4 OTH exome AF: 0.00269

GnomAD4 genome AF: 0.00144 AC: 208 AN: 144430 Hom.: 1 Cov.: 29 AF XY: 0.00196 AC XY: 137 AN XY: 70052

Gnomad4 AFR AF: 0.0000503

Gnomad4 AMR AF: 0.000139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.000689

Gnomad4 OTH AF: 0.000507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199789186; hg19: chr17-42881668;