5-34034708-C-T

Variant names:

• chr5-34034708-C-T
• rs213583
• NM_181435.6:c.415+939G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181435.6(C1QTNF3):​c.415+939G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: C1QTNF3 NM_181435.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF3	NM_181435.6	c.415+939G>A		intron_variant	Intron 2 of 5	ENST00000382065.8	NP_852100.3
C1QTNF3	NM_030945.4	c.196+939G>A		intron_variant	Intron 2 of 5		NP_112207.1
C1QTNF3-AMACR	NR_037951.1	n.223+939G>A		intron_variant	Intron 2 of 8
C1QTNF3	NR_146599.1	n.1006+939G>A		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.415+939G>A		intron_variant	Intron 2 of 5	1	NM_181435.6	ENSP00000371497.3
C1QTNF3	ENST00000231338.7	c.196+939G>A		intron_variant	Intron 2 of 5	1		ENSP00000231338.7
C1QTNF3-AMACR	ENST00000382079.3	n.148+939G>A		intron_variant	Intron 2 of 8	2		ENSP00000371511.3
C1QTNF3	ENST00000508434.1	n.283+939G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.35
DANN	Benign	0.92
PhyloP100		-2.3

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: rs213583; hg19: chr5-34034813;