Genetic Variant C1QTNF4:p.Ala158Pro (chr11-47590339-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031909.3(C1QTNF4):c.472G>C(p.Ala158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,341,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

C1QTNF4
NM_031909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

C1QTNF4 (HGNC:14346): (C1q and TNF related 4) Predicted to enable cytokine activity. Involved in positive regulation of cytokine production and positive regulation of signal transduction. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07480466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF4	NM_031909.3 link	c.472G>C	p.Ala158Pro	missense_variant	Exon 2 of 2	ENST00000302514.4	NP_114115.2	Q9BXJ3A0A3B0J0L9
C1QTNF4	XM_017017166.2 link	c.472G>C	p.Ala158Pro	missense_variant	Exon 3 of 3		XP_016872655.1	Q9BXJ3A0A3B0J0L9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF4	ENST00000302514.4 link	c.472G>C	p.Ala158Pro	missense_variant	Exon 2 of 2	1	NM_031909.3	ENSP00000302274.3		Q9BXJ3
C1QTNF4	ENST00000530097.1 link	c.300+172G>C		intron_variant	Intron 1 of 1	3		ENSP00000434548.1		E9PPZ5

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

148310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000905

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:

0.000980

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1193272

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

577486

show subpopulations

Gnomad4 AFR exome

AF:

0.000357

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000208

GnomAD4 genome

AF:

0.000263

AC:

AN:

148310

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

AN XY:

72250

show subpopulations

Gnomad4 AFR

AF:

0.000905

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:

0.000980

Bravo

AF:

0.000204

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.472G>C (p.A158P) alteration is located in exon 2 (coding exon 1) of the C1QTNF4 gene. This alteration results from a G to C substitution at nucleotide position 472, causing the alanine (A) at amino acid position 158 to be replaced by a proline (P). 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

Benign

0.067

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.17

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.2

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

2.1

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MutPred

0.67

Gain of loop (P = 0.0166);

MVP

0.043

ClinPred

0.67

GERP RS

3.5

Varity_R

0.16

gMVP

0.24

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