Variant 5-34028842-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181435.6(C1QTNF3):c.612G>T(p.Gln204His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Consequence

C1QTNF3
NM_181435.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

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:

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ACMG classification

Classification made for transcript

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=0.34344375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF3	NM_181435.6 linkuse as main transcript	c.612G>T	p.Gln204His	missense_variant	4/6	ENST00000382065.8
C1QTNF3-AMACR	NR_037951.1 linkuse as main transcript	n.420G>T		non_coding_transcript_exon_variant	4/9
C1QTNF3	NM_030945.4 linkuse as main transcript	c.393G>T	p.Gln131His	missense_variant	4/6
C1QTNF3	NR_146599.1 linkuse as main transcript	n.1203G>T		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.612G>T	p.Gln204His	missense_variant	4/6	1	NM_181435.6	P4	Q9BXJ4-3
C1QTNF3	ENST00000231338.7 linkuse as main transcript	c.393G>T	p.Gln131His	missense_variant	4/6	1		A1	Q9BXJ4-1
C1QTNF3	ENST00000513471.5 linkuse as main transcript	n.167G>T		non_coding_transcript_exon_variant	1/3	1
C1QTNF3	ENST00000513065.1 linkuse as main transcript	n.158G>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

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

Jul 19, 2023

The c.612G>T (p.Q204H) alteration is located in exon 4 (coding exon 4) of the C1QTNF3 gene. This alteration results from a G to T substitution at nucleotide position 612, causing the glutamine (Q) at amino acid position 204 to be replaced by a histidine (H). 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

0.61

BayesDel_addAF

Benign

0.0026

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

.;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.57

.;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.23

Sift

Benign

0.080

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.14

.;B

Vest4

0.45

MutPred

0.35

.;Gain of disorder (P = 0.1628);

MVP

0.81

MPC

0.96

ClinPred

0.77

GERP RS

4.7

Varity_R

0.11

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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