17-44804300-TAAAAAA-TAAAAA

Variant names:

• chr17-44804300-TA-T
• rs199789186
• NM_005497.4:c.*326delT

Variant summary

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

The NM_005497.4(GJC1):​c.*326delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 185,928 control chromosomes in the GnomAD database, including 2 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.0022 (1 hom., cov: 29)
  • Exomes 𝑓: 0.12 (1 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.*326delT		3_prime_UTR	Exon 3 of 3	NP_005488.2	P36383
	GJC1	NM_001080383.2		c.*326delT		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.*326delT		3_prime_UTR	Exon 3 of 3	ENSP00000467201.1	P36383
	GJC1	ENST00000330514.4	TSL:2	c.*326delT		3_prime_UTR	Exon 2 of 2	ENSP00000333193.3	P36383
	GJC1	ENST00000590758.3	TSL:3	c.*326delT		3_prime_UTR	Exon 2 of 2	ENSP00000466339.1	P36383

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 311 AN: 143966 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00153

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00199

Gnomad SAS AF: 0.000440

Gnomad FIN AF: 0.00570

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00103

GnomAD4 exome AF: 0.120 AC: 5025 AN: 41908 Hom.: 1 Cov.: 0 AF XY: 0.121 AC XY: 2573 AN XY: 21182

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

African (AFR) AF: 0.108 AC: 146 AN: 1358

American (AMR) AF: 0.133 AC: 302 AN: 2270

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 171 AN: 1512

East Asian (EAS) AF: 0.0984 AC: 240 AN: 2438

South Asian (SAS) AF: 0.119 AC: 124 AN: 1046

European-Finnish (FIN) AF: 0.125 AC: 275 AN: 2204

Middle Eastern (MID) AF: 0.108 AC: 19 AN: 176

European-Non Finnish (NFE) AF: 0.121 AC: 3391 AN: 28054

Other (OTH) AF: 0.125 AC: 357 AN: 2850

⚠️ 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: 0.00219 AC: 316 AN: 144020 Hom.: 1 Cov.: 29 AF XY: 0.00245 AC XY: 171 AN XY: 69826

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

African (AFR) AF: 0.00388 AC: 154 AN: 39676

American (AMR) AF: 0.00153 AC: 22 AN: 14370

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 4 AN: 3386

East Asian (EAS) AF: 0.00200 AC: 10 AN: 5002

South Asian (SAS) AF: 0.000661 AC: 3 AN: 4538

European-Finnish (FIN) AF: 0.00570 AC: 50 AN: 8768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00107 AC: 70 AN: 65158

Other (OTH) AF: 0.00152 AC: 3 AN: 1968

⚠️ 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.

Alfa AF: 0.000454 Hom.: 14

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

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; COSMIC: COSV57910989; COSMIC: COSV57910989;