13-24318824-C-G

Variant names:

• chr13-24318824-C-G
• NM_178540.5:c.173C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_178540.5(C1QTNF9):​c.173C>G​(p.Pro58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73

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]

ENSG00000273167 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue 4-hydroxyproline (size 0) in uniprot entity C1T9A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38670754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF9	NM_178540.5	c.173C>G	p.Pro58Arg	missense_variant	Exon 3 of 4	ENST00000332018.5	NP_848635.2
C1QTNF9	NM_001303137.2	c.173C>G	p.Pro58Arg	missense_variant	Exon 4 of 5		NP_001290066.1
C1QTNF9	NM_001303138.2	c.173C>G	p.Pro58Arg	missense_variant	Exon 3 of 4		NP_001290067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF9	ENST00000332018.5	c.173C>G	p.Pro58Arg	missense_variant	Exon 3 of 4	1	NM_178540.5	ENSP00000333737.4
ENSG00000273167	ENST00000382141.4	n.*169C>G		non_coding_transcript_exon_variant	Exon 15 of 16	5		ENSP00000371576.4
ENSG00000273167	ENST00000382141.4	n.*169C>G		3_prime_UTR_variant	Exon 15 of 16	5		ENSP00000371576.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173C>G (p.P58R) alteration is located in exon 3 (coding exon 2) of the C1QTNF9 gene. This alteration results from a C to G substitution at nucleotide position 173, causing the proline (P) at amino acid position 58 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.27	.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	0.21	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.048	D;D
Sift4G	Benign	0.46	T;T
Polyphen		0.92	P;P
Vest4		0.25
MutPred		0.42		Gain of catalytic residue at P61 (P = 0.0108);Gain of catalytic residue at P61 (P = 0.0108);
MVP		0.87
ClinPred		0.58	D
GERP RS		2.7
Varity_R		0.11
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr13-24892962;