Genetic Variant C1QTNF4:p.Glu268Lys (chr11-47590009-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031909.3(C1QTNF4):c.802G>A(p.Glu268Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

C1QTNF4
NM_031909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Publications

1 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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.868

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.802G>A	p.Glu268Lys	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.802G>A	p.Glu268Lys	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
C1QTNF4	ENST00000862513.1		c.802G>A	p.Glu268Lys	missense	Exon 3 of 3	ENSP00000532572.1
C1QTNF4	ENST00000954826.1		c.802G>A	p.Glu268Lys	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000820

AC:

AN:

243984

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.0000674

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110476

Other (OTH)

AF:

0.00

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.18

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.91

M_CAP

Pathogenic

0.82

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

2.0

PhyloP100

6.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.53

Sift

Benign

0.058

Sift4G

Benign

0.19

Polyphen

0.89

Vest4

0.80

MutPred

0.67

Gain of MoRF binding (P = 0.0019)

MVP

0.75

ClinPred

0.62

GERP RS

3.3

Varity_R

0.30

gMVP

0.90

Mutation Taster

=73/27

polymorphism

(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

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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