5-34043038-T-C

Variant names:

• chr5-34043038-T-C
• NM_181435.6:c.88A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181435.6(C1QTNF3):​c.88A>G​(p.Ser30Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.43

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3141985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF3	NM_181435.6	c.88A>G	p.Ser30Gly	missense_variant	Exon 1 of 6	ENST00000382065.8	NP_852100.3
C1QTNF3	NM_030945.4	c.84+4A>G		splice_region_variant, intron_variant	Intron 1 of 5		NP_112207.1
C1QTNF3-AMACR	NR_037951.1	n.112-7280A>G		intron_variant	Intron 1 of 8
C1QTNF3	NR_146599.1	n.895-7280A>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.88A>G	p.Ser30Gly	missense_variant	Exon 1 of 6	1	NM_181435.6	ENSP00000371497.3
C1QTNF3	ENST00000231338.7	c.84+4A>G		splice_region_variant, intron_variant	Intron 1 of 5	1		ENSP00000231338.7
C1QTNF3-AMACR	ENST00000382079.3	n.37-7280A>G		intron_variant	Intron 1 of 8	2		ENSP00000371511.3
C1QTNF3	ENST00000508434.1	n.171+4A>G		splice_region_variant, 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

Nov 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88A>G (p.S30G) 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 88, causing the serine (S) at amino acid position 30 to be replaced by a glycine (G). 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	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.043	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.19	T
Vest4		0.28
MutPred		0.28		Loss of sheet (P = 0.0104);
MVP		0.88
MPC		0.39
ClinPred		0.92	D
GERP RS		5.6
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr5-34043143;