11-47589847-C-A

Variant summary

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

The NM_031909.3(C1QTNF4):​c.964G>T​(p.Gly322Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,547,098 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G322V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

C1QTNF4
NM_031909.3 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47
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]

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=0.19672975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1QTNF4NM_031909.3 linkc.964G>T p.Gly322Cys missense_variant Exon 2 of 2 ENST00000302514.4 NP_114115.2 Q9BXJ3A0A3B0J0L9
C1QTNF4XM_017017166.2 linkc.964G>T p.Gly322Cys missense_variant Exon 3 of 3 XP_016872655.1 Q9BXJ3A0A3B0J0L9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1QTNF4ENST00000302514.4 linkc.964G>T p.Gly322Cys missense_variant Exon 2 of 2 1 NM_031909.3 ENSP00000302274.3 Q9BXJ3
C1QTNF4ENST00000530097 linkc.*204G>T 3_prime_UTR_variant Exon 2 of 2 3 ENSP00000434548.1 E9PPZ5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152024
Hom.:
0
Cov.:
33
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:
0.000195
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:
0.0000133
AC:
2
AN:
149996
Hom.:
0
AF XY:
0.0000251
AC XY:
2
AN XY:
79672
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000186
Gnomad SAS 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:
0.00000215
AC:
3
AN:
1395074
Hom.:
0
Cov.:
32
AF XY:
0.00000291
AC XY:
2
AN XY:
687888
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000844
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152024
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.964G>T (p.G322C) alteration is located in exon 2 (coding exon 1) of the C1QTNF4 gene. This alteration results from a G to T substitution at nucleotide position 964, causing the glycine (G) at amino acid position 322 to be replaced by a cysteine (C). 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
0.21
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.23
N
M_CAP
Pathogenic
0.64
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.54
N
REVEL
Benign
0.20
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.021
D
Polyphen
0.22
B
Vest4
0.34
MutPred
0.29
Loss of disorder (P = 0.0043);
MVP
0.47
ClinPred
0.32
T
GERP RS
4.4
Varity_R
0.20
gMVP
0.58

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.

Other links and lift over

dbSNP: rs1436958297; hg19: chr11-47611399; API