chr17-79047616-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030968.5(C1QTNF1):​c.374C>T​(p.Thr125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,434,268 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: not found (cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

C1QTNF1
NM_030968.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.388
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04456064).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1QTNF1NM_030968.5 linkc.374C>T p.Thr125Ile missense_variant Exon 4 of 4 ENST00000579760.6 NP_112230.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1QTNF1ENST00000579760.6 linkc.374C>T p.Thr125Ile missense_variant Exon 4 of 4 1 NM_030968.5 ENSP00000463922.1 Q9BXJ1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000429
AC:
1
AN:
233116
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
125880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000938
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000418
AC:
6
AN:
1434268
Hom.:
0
Cov.:
32
AF XY:
0.00000563
AC XY:
4
AN XY:
710468
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000365
Gnomad4 OTH exome
AF:
0.0000339
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.374C>T (p.T125I) alteration is located in exon 4 (coding exon 3) of the C1QTNF1 gene. This alteration results from a C to T substitution at nucleotide position 374, causing the threonine (T) at amino acid position 125 to be replaced by an isoleucine (I). 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
0.066
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
2.1
DANN
Benign
0.91
DEOGEN2
Benign
0.030
T;T;T;T;T;T;T;T;T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.36
.;T;.;.;.;T;.;.;.;.
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.045
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
0.34
.;N;N;N;N;.;N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.3
.;.;.;.;N;N;.;.;.;.
REVEL
Benign
0.27
Sift
Benign
0.28
.;.;.;.;T;T;.;.;.;.
Sift4G
Benign
0.21
T;T;T;T;T;T;T;T;T;T
Polyphen
0.0010
.;B;B;B;B;.;B;B;B;B
Vest4
0.11
MutPred
0.31
.;Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);.;Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);Loss of phosphorylation at T125 (P = 0.0175);
MVP
0.59
MPC
0.31
ClinPred
0.033
T
GERP RS
-5.7
Varity_R
0.036
gMVP
0.10

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: rs138383380; hg19: chr17-77043698; API