5-34042761-AAAC-AAACAAC

Variant names:

• chr5-34042761-A-AAAC
• rs57826552
• NM_181435.6:c.303+59_303+61dupGTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_181435.6(C1QTNF3):​c.303+59_303+61dupGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,460,992 control chromosomes in the GnomAD database, including 29,603 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6183 hom., cov: 23)
  • Exomes 𝑓: 0.18 (23420 hom.)
• Consequence: C1QTNF3 NM_181435.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 3 publications found

Genes affected

C1QTNF3 (HGNC:14326): (C1q and TNF related 3) Enables identical protein binding activity. Involved in several processes, including cellular triglyceride homeostasis; negative regulation of NIK/NF-kappaB signaling; and regulation of cytokine production. Acts upstream of or within negative regulation of gluconeogenesis. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF3-AMACR (HGNC:49198): (C1QTNF3-AMACR readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C1q and tumor necrosis factor related protein 3 (C1QTNF3) and alpha-methylacyl-CoA racemase (AMACR) genes on chromosome 5. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not likely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181435.6. 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
	C1QTNF3	NM_181435.6	MANE Select	c.303+59_303+61dupGTT		intron	N/A	NP_852100.3	Q9BXJ4-3
	C1QTNF3	NM_030945.4		c.84+278_84+280dupGTT		intron	N/A	NP_112207.1	Q9BXJ4-1
	C1QTNF3-AMACR	NR_037951.1		n.112-7006_112-7004dupGTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF3	ENST00000382065.8	TSL:1 MANE Select	c.303+61_303+62insGTT		intron	N/A	ENSP00000371497.3	Q9BXJ4-3
	C1QTNF3	ENST00000231338.7	TSL:1	c.84+280_84+281insGTT		intron	N/A	ENSP00000231338.7	Q9BXJ4-1
	C1QTNF3-AMACR	ENST00000382079.3	TSL:2	n.37-7004_37-7003insGTT		intron	N/A	ENSP00000371511.3	E9PGA6

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39087 AN: 151650 Hom.: 6163 Cov.: 23

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.177 AC: 232110 AN: 1309222 Hom.: 23420 AF XY: 0.181 AC XY: 117223 AN XY: 646854

African (AFR) AF: 0.428 AC: 11918 AN: 27838

American (AMR) AF: 0.244 AC: 7465 AN: 30640

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 3746 AN: 20458

East Asian (EAS) AF: 0.425 AC: 16148 AN: 38018

South Asian (SAS) AF: 0.336 AC: 23292 AN: 69392

European-Finnish (FIN) AF: 0.173 AC: 8717 AN: 50354

Middle Eastern (MID) AF: 0.276 AC: 1118 AN: 4052

European-Non Finnish (NFE) AF: 0.146 AC: 148597 AN: 1014394

Other (OTH) AF: 0.205 AC: 11109 AN: 54076

GnomAD4 genome AF: 0.258 AC: 39144 AN: 151770 Hom.: 6183 Cov.: 23 AF XY: 0.260 AC XY: 19265 AN XY: 74160

African (AFR) AF: 0.438 AC: 18093 AN: 41280

American (AMR) AF: 0.216 AC: 3296 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3458

East Asian (EAS) AF: 0.410 AC: 2109 AN: 5142

South Asian (SAS) AF: 0.344 AC: 1649 AN: 4790

European-Finnish (FIN) AF: 0.177 AC: 1866 AN: 10568

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10698 AN: 67948

Other (OTH) AF: 0.240 AC: 505 AN: 2106

Alfa AF: 0.0543 Hom.: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs57826552;

hg19: chr5-34042866;