5-34035666-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_181435.6(C1QTNF3):c.396G>A(p.Pro132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,610,846 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: C1QTNF3 NM_181435.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.62

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:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-34035666-C-T is Benign according to our data. Variant chr5-34035666-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.62 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF3	NM_181435.6	c.396G>A	p.Pro132=	synonymous_variant	2/6	ENST00000382065.8
C1QTNF3-AMACR	NR_037951.1	n.204G>A		non_coding_transcript_exon_variant	2/9
C1QTNF3	NM_030945.4	c.177G>A	p.Pro59=	synonymous_variant	2/6
C1QTNF3	NR_146599.1	n.987G>A		non_coding_transcript_exon_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.396G>A	p.Pro132=	synonymous_variant	2/6	1	NM_181435.6	P4
C1QTNF3	ENST00000231338.7	c.177G>A	p.Pro59=	synonymous_variant	2/6	1		A1
C1QTNF3	ENST00000508434.1	n.264G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000113 AC: 28 AN: 247664 Hom.: 0 AF XY: 0.000134 AC XY: 18 AN XY: 134162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000266

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000141 AC: 206 AN: 1458488 Hom.: 2 Cov.: 31 AF XY: 0.000150 AC XY: 109 AN XY: 725706

Gnomad4 AFR exome AF: 0.000241

Gnomad4 AMR exome AF: 0.0000913

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000774

Gnomad4 OTH exome AF: 0.000465

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74506

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000907

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

C1QTNF3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.66
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs140166139; hg19: chr5-34035771;