5-34042845-T-C

Variant names:

• chr5-34042845-T-C
• NM_181435.6:c.281A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181435.6(C1QTNF3):​c.281A>G​(p.Gln94Arg) variant causes a missense 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QTNF3 NM_181435.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18736893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF3	NM_181435.6	c.281A>G	p.Gln94Arg	missense_variant	Exon 1 of 6	ENST00000382065.8	NP_852100.3
C1QTNF3	NM_030945.4	c.84+197A>G		intron_variant	Intron 1 of 5		NP_112207.1
C1QTNF3-AMACR	NR_037951.1	n.112-7087A>G		intron_variant	Intron 1 of 8
C1QTNF3	NR_146599.1	n.895-7087A>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.281A>G	p.Gln94Arg	missense_variant	Exon 1 of 6	1	NM_181435.6	ENSP00000371497.3
C1QTNF3	ENST00000231338.7	c.84+197A>G		intron_variant	Intron 1 of 5	1		ENSP00000231338.7
C1QTNF3-AMACR	ENST00000382079.3	n.37-7087A>G		intron_variant	Intron 1 of 8	2		ENSP00000371511.3
C1QTNF3	ENST00000508434.1	n.171+197A>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.281A>G (p.Q94R) alteration is located in exon 1 (coding exon 1) of the C1QTNF3 gene. This alteration results from a A to G substitution at nucleotide position 281, causing the glutamine (Q) at amino acid position 94 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.60	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.24
Sift	Benign	0.064	T
Sift4G	Benign	0.50	T
Vest4		0.15
MutPred		0.51		Gain of helix (P = 0.132);
MVP		0.71
MPC		0.43
ClinPred		0.69	D
GERP RS		4.4
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-34042950; COSMIC: COSV99180686;