5-34042975-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181435.6(C1QTNF3):c.151G>A(p.Gly51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (1 hom.)
• Consequence: C1QTNF3 NM_181435.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04320386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF3	NM_181435.6	c.151G>A	p.Gly51Ser	missense_variant	1/6	ENST00000382065.8
C1QTNF3-AMACR	NR_037951.1	n.112-7217G>A		intron_variant, non_coding_transcript_variant
C1QTNF3	NM_030945.4	c.84+67G>A		intron_variant
C1QTNF3	NR_146599.1	n.895-7217G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.151G>A	p.Gly51Ser	missense_variant	1/6	1	NM_181435.6	P4
C1QTNF3	ENST00000231338.7	c.84+67G>A		intron_variant		1		A1
C1QTNF3	ENST00000508434.1	n.171+67G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

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

GnomAD3 exomes AF: 0.0000717 AC: 18 AN: 251054 Hom.: 1 AF XY: 0.0000884 AC XY: 12 AN XY: 135670

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1461880 Hom.: 1 Cov.: 31 AF XY: 0.0000371 AC XY: 27 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74474

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.151G>A (p.G51S) alteration is located in exon 1 (coding exon 1) of the C1QTNF3 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glycine (G) at amino acid position 51 to be replaced by a serine (S). 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	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	16
Dann	Uncertain	1.0
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.084
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.056	T
Vest4		0.14
MVP		0.30
MPC		0.36
ClinPred		0.038	T
GERP RS		2.5
gMVP		0.22

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: rs200960868; hg19: chr5-34043080; COSMIC: COSV51468561;