Variant 5-34028802-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_181435.6(C1QTNF3):c.652G>C(p.Gly218Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,460,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

C1QTNF3
NM_181435.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

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 links:

C1QTNF3-AMACR (HGNC:):

C1QTNF3-AMACR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF3	NM_181435.6 linkuse as main transcript	c.652G>C	p.Gly218Arg	missense_variant	4/6	ENST00000382065.8
C1QTNF3-AMACR	NR_037951.1 linkuse as main transcript	n.460G>C		non_coding_transcript_exon_variant	4/9
C1QTNF3	NM_030945.4 linkuse as main transcript	c.433G>C	p.Gly145Arg	missense_variant	4/6
C1QTNF3	NR_146599.1 linkuse as main transcript	n.1243G>C		non_coding_transcript_exon_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF3	ENST00000382065.8 linkuse as main transcript	c.652G>C	p.Gly218Arg	missense_variant	4/6	1	NM_181435.6	P4	Q9BXJ4-3
C1QTNF3	ENST00000231338.7 linkuse as main transcript	c.433G>C	p.Gly145Arg	missense_variant	4/6	1		A1	Q9BXJ4-1
C1QTNF3	ENST00000513471.5 linkuse as main transcript	n.207G>C		non_coding_transcript_exon_variant	1/3	1
C1QTNF3	ENST00000513065.1 linkuse as main transcript	n.198G>C		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250132

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1460128

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.652G>C (p.G218R) alteration is located in exon 4 (coding exon 4) of the C1QTNF3 gene. This alteration results from a G to C substitution at nucleotide position 652, causing the glycine (G) at amino acid position 218 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

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.36

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

0.54

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-7.6

D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.025

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.97

.;D

Vest4

0.84

MutPred

0.69

.;Gain of solvent accessibility (P = 0.1014);

MVP

0.97

MPC

1.2

ClinPred

0.86

GERP RS

5.6

Varity_R

0.62

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over