5-34020253-T-C

Position:

• chr5-34020253-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181435.6(C1QTNF3):​c.*330A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 206,664 control chromosomes in the GnomAD database, including 22,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16796 hom., cov: 32)
  • Exomes 𝑓: 0.45 (5944 hom.)
• Consequence: C1QTNF3 NM_181435.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QTNF3	NM_181435.6	c.*330A>G		3_prime_UTR_variant	6/6	ENST00000382065.8	NP_852100.3
C1QTNF3	NM_030945.4	c.*330A>G		3_prime_UTR_variant	6/6		NP_112207.1
C1QTNF3	NR_146599.1	n.1881A>G		non_coding_transcript_exon_variant	12/12
C1QTNF3-AMACR	NR_037951.1	n.764+334A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QTNF3	ENST00000382065	c.*330A>G		3_prime_UTR_variant	6/6	1	NM_181435.6	ENSP00000371497.3
C1QTNF3-AMACR	ENST00000382079.3	n.689+334A>G		intron_variant		2		ENSP00000371511.3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69940 AN: 151876 Hom.: 16765 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.452 AC: 24707 AN: 54670 Hom.: 5944 Cov.: 0 AF XY: 0.462 AC XY: 13201 AN XY: 28548

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.461 AC: 70022 AN: 151994 Hom.: 16796 Cov.: 32 AF XY: 0.463 AC XY: 34386 AN XY: 74284

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.502

Alfa AF: 0.403 Hom.: 12223

Bravo AF: 0.474

Asia WGS AF: 0.635 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs840385; hg19: chr5-34020358;