Variant 13-24321218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_178540.5(C1QTNF9):c.452C>T(p.Pro151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,322,434 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

C1QTNF9
NM_178540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.209

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 -6 ACMG points.

PM1

In a modified_residue 4-hydroxyproline (size 0) in uniprot entity C1T9A_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.023137927).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF9	NM_178540.5 linkuse as main transcript	c.452C>T	p.Pro151Leu	missense_variant	4/4	ENST00000332018.5
C1QTNF9	NM_001303137.2 linkuse as main transcript	c.452C>T	p.Pro151Leu	missense_variant	5/5
C1QTNF9	NM_001303138.2 linkuse as main transcript	c.452C>T	p.Pro151Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C1QTNF9	ENST00000332018.5 linkuse as main transcript	c.452C>T	p.Pro151Leu	missense_variant	4/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1 linkuse as main transcript	n.73+308G>A		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6 linkuse as main transcript	c.452C>T	p.Pro151Leu	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000272

AC:

AN:

106468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

Gnomad ASJ

AF:

0.000409

Gnomad EAS

AF:

0.00436

Gnomad SAS

AF:

0.00120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000434

Gnomad OTH

AF:

0.000698

GnomAD3 exomes

AF:

0.000585

AC:

AN:

112734

Hom.:

AF XY:

0.000566

AC XY:

AN XY:

60092

show subpopulations

Gnomad AFR exome

AF:

0.0000950

Gnomad AMR exome

AF:

0.0000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00534

Gnomad SAS exome

AF:

0.000136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000640

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000240

AC:

292

AN:

1215894

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

156

AN XY:

601624

show subpopulations

Gnomad4 AFR exome

AF:

0.000101

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00482

Gnomad4 SAS exome

AF:

0.000247

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000734

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000272

AC:

AN:

106540

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

AN XY:

49972

show subpopulations

Gnomad4 AFR

AF:

0.0000591

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.000409

Gnomad4 EAS

AF:

0.00437

Gnomad4 SAS

AF:

0.00121

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000434

Gnomad4 OTH

AF:

0.000695

Alfa

AF:

0.000371

Hom.:

ExAC

AF:

0.000128

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

Aug 08, 2023

The c.452C>T (p.P151L) 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 452, causing the proline (P) at amino acid position 151 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

0.067

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.23

CADD

Benign

9.2

DANN

Benign

0.60

DEOGEN2

Uncertain

0.43

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.082

M_CAP

Benign

0.058

MetaRNN

Benign

0.023

T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.25

Sift

Benign

0.073

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0040

B;B

Vest4

0.19

MutPred

0.37

Gain of catalytic residue at L150 (P = 5e-04);Gain of catalytic residue at L150 (P = 5e-04);

MVP

0.57

ClinPred

0.012

GERP RS

-0.29

Varity_R

0.067

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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