Variant 13-24321298-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_178540.5(C1QTNF9):c.532C>T(p.Arg178Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C1QTNF9
NM_178540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

C1QTNF9 (HGNC:28732): (C1q and TNF related 9) Enables identical protein binding activity. Predicted to be involved in signal transduction. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF9 links:

C1QTNF9-AS1 (HGNC:39906): (C1QTNF9 antisense RNA 1)

C1QTNF9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2790258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF9	NM_178540.5 linkuse as main transcript	c.532C>T	p.Arg178Trp	missense_variant	4/4	ENST00000332018.5
C1QTNF9	NM_001303137.2 linkuse as main transcript	c.532C>T	p.Arg178Trp	missense_variant	5/5
C1QTNF9	NM_001303138.2 linkuse as main transcript	c.532C>T	p.Arg178Trp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C1QTNF9	ENST00000332018.5 linkuse as main transcript	c.532C>T	p.Arg178Trp	missense_variant	4/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1 linkuse as main transcript	n.73+228G>A		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6 linkuse as main transcript	c.532C>T	p.Arg178Trp	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000325

AC:

AN:

122960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000827

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000882

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000198

AC:

AN:

201846

Hom.:

AF XY:

0.00000916

AC XY:

AN XY:

109206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000624

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000345

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000148

AC:

AN:

1418420

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

703604

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000147

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000325

AC:

AN:

122960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57918

show subpopulations

Gnomad4 AFR

AF:

0.0000827

Gnomad4 AMR

AF:

0.0000882

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.532C>T (p.R178W) alteration is located in exon 4 (coding exon 3) of the C1QTNF9 gene. This alteration results from a C to T substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;D

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.77

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.28

T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.82

N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.24

B;B

Vest4

0.30

MutPred

0.49

Gain of catalytic residue at R178 (P = 6e-04);Gain of catalytic residue at R178 (P = 6e-04);

MVP

0.76

ClinPred

0.97

GERP RS

-0.43

Varity_R

0.74

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over