Genetic Variant C1QTNF4:p.Gly281Arg (chr11-47589970-C-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_031909.3(C1QTNF4):c.841G>C(p.Gly281Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G281S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

C1QTNF4
NM_031909.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.96

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031909.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF4	NM_031909.3	MANE Select	c.841G>C	p.Gly281Arg	missense	Exon 2 of 2	NP_114115.2	Q9BXJ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QTNF4	ENST00000302514.4	TSL:1 MANE Select	c.841G>C	p.Gly281Arg	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
C1QTNF4	ENST00000862513.1		c.841G>C	p.Gly281Arg	missense	Exon 3 of 3	ENSP00000532572.1
C1QTNF4	ENST00000954826.1		c.841G>C	p.Gly281Arg	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.71

MutationAssessor

Pathogenic

3.3

PhyloP100

6.0

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.1

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.68

MutPred

0.83

Gain of MoRF binding (P = 0.0499)

MVP

0.85

ClinPred

1.0

GERP RS

4.3

Varity_R

0.72

gMVP

0.94

Mutation Taster

=38/62

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over