chr13-24321298-C-T

Variant names:

• chr13-24321298-C-T
• rs780133616
• NM_178540.5:c.532C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_178540.5(C1QTNF9):​c.532C>T​(p.Arg178Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2790258).

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.532C>T	p.Arg178Trp	missense	Exon 4 of 4	NP_848635.2	P0C862
	C1QTNF9	NM_001303137.2		c.532C>T	p.Arg178Trp	missense	Exon 5 of 5	NP_001290066.1	P0C862
	C1QTNF9	NM_001303138.2		c.532C>T	p.Arg178Trp	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.532C>T	p.Arg178Trp	missense	Exon 4 of 4	ENSP00000333737.4	P0C862
	C1QTNF9	ENST00000382071.6	TSL:5	c.532C>T	p.Arg178Trp	missense	Exon 4 of 4	ENSP00000371503.2	P0C862
	C1QTNF9	ENST00000875261.1		c.532C>T	p.Arg178Trp	missense	Exon 5 of 5	ENSP00000545320.1

Frequencies

GnomAD3 genomes AF: 0.0000325 AC: 4 AN: 122960 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0000827

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000882

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000198 AC: 4 AN: 201846 AF XY: 0.00000916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000624

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000345

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000148 AC: 21 AN: 1418420 Hom.: 0 Cov.: 33 AF XY: 0.0000114 AC XY: 8 AN XY: 703604

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000302 AC: 1 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 42158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38838

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.0000147 AC: 16 AN: 1084800

Other (OTH) AF: 0.0000340 AC: 2 AN: 58740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000229138), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000325 AC: 4 AN: 122960 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 57918

African (AFR) AF: 0.0000827 AC: 3 AN: 36260

American (AMR) AF: 0.0000882 AC: 1 AN: 11338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2814

East Asian (EAS) AF: 0.00 AC: 0 AN: 4288

South Asian (SAS) AF: 0.00 AC: 0 AN: 3560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55706

Other (OTH) AF: 0.00 AC: 0 AN: 1604

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000251 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.24	B
Vest4		0.30
MutPred		0.49		Gain of catalytic residue at R178 (P = 6e-04)
MVP		0.76
ClinPred		0.97	D
GERP RS		-0.43
Varity_R		0.74
gMVP		0.67
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs780133616; hg19: chr13-24895436;