17-44804300-TAAAAAA-TAAAAAAAAA

Variant names:

• chr17-44804300-T-TAAA
• rs199789186
• NM_005497.4:c.*324_*326dupTTT

Variant summary

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

The NM_005497.4(GJC1):​c.*324_*326dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 44,240 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: not found (cov: 29)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: GJC1 NM_005497.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963
• 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.*324_*326dupTTT		3_prime_UTR	Exon 3 of 3	NP_005488.2	P36383
	GJC1	NM_001080383.2		c.*324_*326dupTTT		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.*324_*326dupTTT		3_prime_UTR	Exon 3 of 3	ENSP00000467201.1	P36383
	GJC1	ENST00000330514.4	TSL:2	c.*324_*326dupTTT		3_prime_UTR	Exon 2 of 2	ENSP00000333193.3	P36383
	GJC1	ENST00000590758.3	TSL:3	c.*324_*326dupTTT		3_prime_UTR	Exon 2 of 2	ENSP00000466339.1	P36383

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.000136 AC: 6 AN: 44240 Hom.: 0 Cov.: 0 AF XY: 0.0000895 AC XY: 2 AN XY: 22342

⚠️ 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: 0.00 AC: 0 AN: 2386

Ashkenazi Jewish (ASJ) AF: 0.000620 AC: 1 AN: 1612

East Asian (EAS) AF: 0.00 AC: 0 AN: 2556

South Asian (SAS) AF: 0.00 AC: 0 AN: 1082

European-Finnish (FIN) AF: 0.000861 AC: 2 AN: 2324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.000101 AC: 3 AN: 29680

Other (OTH) AF: 0.00 AC: 0 AN: 2990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000559552), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs199789186; hg19: chr17-42881668;