13-24321070-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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

ACMG classification

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/exons	MANE	UniProt
C1QTNF9	NM_178540.5	c.304C>T	p.Pro102Ser	missense_variant	4/4	ENST00000332018.5
C1QTNF9	NM_001303137.2	c.304C>T	p.Pro102Ser	missense_variant	5/5
C1QTNF9	NM_001303138.2	c.304C>T	p.Pro102Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF9	ENST00000332018.5	c.304C>T	p.Pro102Ser	missense_variant	4/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1	n.73+456G>A		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6	c.304C>T	p.Pro102Ser	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.54e-7 AC: 1 AN: 1325926 Hom.: 0 Cov.: 27 AF XY: 0.00000151 AC XY: 1 AN XY: 661716

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.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

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	D
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.51	T
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	D
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.

Other links and lift over

hg19: chr13-24895208;