Genetic Variant C1QTNF9:p.Pro102Ser (chr13-24321070-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_178540.5(C1QTNF9):c.304C>T(p.Pro102Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 7.5e-7 ( 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: 4.36

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:

PCOTHP1 (HGNC:39840):

PCOTHP1 links:

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

C1QTNF9-AS1 links:

ENSG00000273167 (HGNC:):

ENSG00000273167 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF9	NM_178540.5 link	c.304C>T	p.Pro102Ser	missense_variant	Exon 4 of 4	ENST00000332018.5	NP_848635.2	P0C862A0A3B0J259
C1QTNF9	NM_001303137.2 link	c.304C>T	p.Pro102Ser	missense_variant	Exon 5 of 5		NP_001290066.1	P0C862A0A3B0J259
C1QTNF9	NM_001303138.2 link	c.304C>T	p.Pro102Ser	missense_variant	Exon 4 of 4		NP_001290067.1	P0C862A0A3B0J259
PCOTHP1		n.24321070C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C1QTNF9	ENST00000332018.5 link	c.304C>T	p.Pro102Ser	missense_variant	Exon 4 of 4	1	NM_178540.5	ENSP00000333737.4	P0C862
C1QTNF9	ENST00000382071.6 link	c.304C>T	p.Pro102Ser	missense_variant	Exon 4 of 4	5		ENSP00000371503.2	P0C862
C1QTNF9-AS1	ENST00000449656.1 link	n.73+456G>A		intron_variant	Intron 1 of 1	5
ENSG00000273167	ENST00000382141.4 link	n.*300C>T		downstream_gene_variant		5		ENSP00000371576.4	A0A0A0MRY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.54e-7

AC:

AN:

1325926

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

661716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000267

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.304C>T (p.P102S) 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 304, causing the proline (P) at amino acid position 102 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.49

Sift

Benign

0.080

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.98

D;D

Vest4

0.63

MutPred

0.28

Gain of catalytic residue at K103 (P = 0.0048);Gain of catalytic residue at K103 (P = 0.0048);

MVP

0.88

ClinPred

0.88

GERP RS

4.1

Varity_R

0.10

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over