13-24321356-T-G

Variant names:

• chr13-24321356-T-G
• rs776164635
• NM_178540.5:c.590T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178540.5(C1QTNF9):​c.590T>G​(p.Leu197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L197P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

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]

PCOTHP1 (HGNC:39840):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.094257).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178540.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF9	NM_178540.5	MANE Select	c.590T>G	p.Leu197Arg	missense	Exon 4 of 4	NP_848635.2	P0C862
	C1QTNF9	NM_001303137.2		c.590T>G	p.Leu197Arg	missense	Exon 5 of 5	NP_001290066.1	P0C862
	C1QTNF9	NM_001303138.2		c.590T>G	p.Leu197Arg	missense	Exon 4 of 4	NP_001290067.1	P0C862

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF9	ENST00000332018.5	TSL:1 MANE Select	c.590T>G	p.Leu197Arg	missense	Exon 4 of 4	ENSP00000333737.4	P0C862
	C1QTNF9	ENST00000382071.6	TSL:5	c.590T>G	p.Leu197Arg	missense	Exon 4 of 4	ENSP00000371503.2	P0C862
	C1QTNF9	ENST00000875261.1		c.590T>G	p.Leu197Arg	missense	Exon 5 of 5	ENSP00000545320.1

Frequencies

GnomAD3 genomes AF: 0.00000696 AC: 1 AN: 143670 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457524 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724746

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108696

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000696 AC: 1 AN: 143670 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 69232

African (AFR) AF: 0.00 AC: 0 AN: 39724

American (AMR) AF: 0.00 AC: 0 AN: 13880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3344

East Asian (EAS) AF: 0.00 AC: 0 AN: 4906

South Asian (SAS) AF: 0.00 AC: 0 AN: 4220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65488

Other (OTH) AF: 0.00 AC: 0 AN: 1910

Alfa AF: 0.000447 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.19
Sift	Benign	0.20	T
Sift4G	Benign	0.37	T
Polyphen		0.0060	B
Vest4		0.15
MutPred		0.49		Gain of MoRF binding (P = 0.0106)
MVP		0.53
ClinPred		0.094	T
GERP RS		3.1
Varity_R		0.088
gMVP		0.70
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs776164635; hg19: chr13-24895494;