13-24321550-G-C

Position:

• chr13-24321550-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178540.5(C1QTNF9):​c.784G>C​(p.Val262Leu) 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. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16564679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF9	NM_178540.5	c.784G>C	p.Val262Leu	missense_variant	4/4	ENST00000332018.5
C1QTNF9	NM_001303137.2	c.784G>C	p.Val262Leu	missense_variant	5/5
C1QTNF9	NM_001303138.2	c.784G>C	p.Val262Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF9	ENST00000332018.5	c.784G>C	p.Val262Leu	missense_variant	4/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1	n.49C>G		non_coding_transcript_exon_variant	1/2	5
C1QTNF9	ENST00000382071.6	c.784G>C	p.Val262Leu	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

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 13, 2022

The c.784G>C (p.V262L) alteration is located in exon 4 (coding exon 3) of the C1QTNF9 gene. This alteration results from a G to C substitution at nucleotide position 784, causing the valine (V) at amino acid position 262 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	0.32
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.093	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.67	D;D;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.12
Sift	Benign	0.16	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0010	B;B
Vest4		0.36
MutPred		0.56		Gain of catalytic residue at Q263 (P = 0.0029);Gain of catalytic residue at Q263 (P = 0.0029);
MVP		0.64
ClinPred		0.29	T
GERP RS		1.2
Varity_R		0.17
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-24895688;