Genetic Variant C1QTNF4:p.Asp215Asn (chr11-47590168-C-T) – 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.643G>A(p.Asp215Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000145 in 1,600,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D215A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

C1QTNF4
NM_031909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

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:

Genome browser will be placed here

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=0.15834075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF4	NM_031909.3 link	c.643G>A	p.Asp215Asn	missense_variant	Exon 2 of 2	ENST00000302514.4	NP_114115.2	Q9BXJ3A0A3B0J0L9
C1QTNF4	XM_017017166.2 link	c.643G>A	p.Asp215Asn	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.643G>A	p.Asp215Asn	missense_variant	Exon 2 of 2	1	NM_031909.3	ENSP00000302274.3		Q9BXJ3
C1QTNF4	ENST00000530097.1 link	c.301-117G>A		intron_variant	Intron 1 of 1	3		ENSP00000434548.1		E9PPZ5

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

220242

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

122482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000628

Gnomad ASJ exome

AF:

0.000323

Gnomad EAS exome

AF:

0.0000599

Gnomad SAS exome

AF:

0.000103

Gnomad FIN exome

AF:

0.000164

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000145

AC:

210

AN:

1449452

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

721072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000466

Gnomad4 ASJ exome

AF:

0.000426

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000199

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.000144

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000145

AC:

AN:

151420

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73886

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000369

AC:

ExAC

AF:

0.000151

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.643G>A (p.D215N) alteration is located in exon 2 (coding exon 1) of the C1QTNF4 gene. This alteration results from a G to A substitution at nucleotide position 643, causing the aspartic acid (D) at amino acid position 215 to be replaced by an asparagine (N). 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.60

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.74

MutationAssessor

Benign

-0.46

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.90

REVEL

Benign

0.27

Sift

Benign

0.93

Sift4G

Benign

1.0

Polyphen

0.16

Vest4

0.16

MVP

0.39

ClinPred

0.071

GERP RS

4.3

Varity_R

0.088

gMVP

0.39

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