chr17-79044102-C-T

Variant summary

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

The NM_030968.5(C1QTNF1):​c.134C>T​(p.Ser45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,611,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

C1QTNF1
NM_030968.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.404
Variant links:
Genes affected
C1QTNF1 (HGNC:14324): (C1q and TNF related 1) Enables collagen binding activity. Involved in several processes, including negative regulation of platelet aggregation; positive regulation of aldosterone secretion; and positive regulation of cytosolic calcium ion concentration. Located in extracellular space. Is integral component of plasma membrane. [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=0.07148063).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1QTNF1NM_030968.5 linkc.134C>T p.Ser45Leu missense_variant Exon 2 of 4 ENST00000579760.6 NP_112230.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1QTNF1ENST00000579760.6 linkc.134C>T p.Ser45Leu missense_variant Exon 2 of 4 1 NM_030968.5 ENSP00000463922.1 Q9BXJ1-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248650
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134466
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000625
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000528
AC:
77
AN:
1459154
Hom.:
0
Cov.:
34
AF XY:
0.0000579
AC XY:
42
AN XY:
725528
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000666
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000989
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
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
Nov 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.S45L) alteration is located in exon 2 (coding exon 1) of the C1QTNF1 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the serine (S) at amino acid position 45 to be replaced by a leucine (L). 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
0.068
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
13
DANN
Benign
0.69
DEOGEN2
Benign
0.022
T;T;T;T;T;T;T;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.52
T;.;.;.;.;.;.;.
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.071
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.69
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.50
.;.;.;N;.;.;.;.
REVEL
Benign
0.089
Sift
Benign
0.35
.;.;.;T;.;.;.;.
Sift4G
Benign
0.45
T;T;T;T;T;T;T;T
Polyphen
0.25
B;B;B;B;B;B;B;B
Vest4
0.14
MVP
0.69
MPC
0.26
ClinPred
0.038
T
GERP RS
1.4
Varity_R
0.034
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs760839700; hg19: chr17-77040184; API