13-24321272-C-T

Variant names:

• chr13-24321272-C-T
• rs536592072
• NM_178540.5:c.506C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178540.5(C1QTNF9):​c.506C>T​(p.Thr169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,435,270 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00012 (3 hom.)
• Consequence: C1QTNF9 NM_178540.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92
• 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)

ENSG00000273167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012411267).
• BP6: Variant 13-24321272-C-T is Benign according to our data. Variant chr13-24321272-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2391165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.506C>T	p.Thr169Met	missense	Exon 4 of 4	NP_848635.2	P0C862
	C1QTNF9	NM_001303137.2		c.506C>T	p.Thr169Met	missense	Exon 5 of 5	NP_001290066.1	P0C862
	C1QTNF9	NM_001303138.2		c.506C>T	p.Thr169Met	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.506C>T	p.Thr169Met	missense	Exon 4 of 4	ENSP00000333737.4	P0C862
	C1QTNF9	ENST00000382071.6	TSL:5	c.506C>T	p.Thr169Met	missense	Exon 4 of 4	ENSP00000371503.2	P0C862
	C1QTNF9	ENST00000875261.1		c.506C>T	p.Thr169Met	missense	Exon 5 of 5	ENSP00000545320.1

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 23 AN: 116336 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00268

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00198

GnomAD2 exomes AF: 0.000261 AC: 43 AN: 164676 AF XY: 0.000239

Gnomad AFR exome AF: 0.0000758

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00245

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00140

GnomAD4 exome AF: 0.000116 AC: 153 AN: 1318844 Hom.: 3 Cov.: 32 AF XY: 0.000112 AC XY: 73 AN XY: 652476

African (AFR) AF: 0.000187 AC: 6 AN: 32044

American (AMR) AF: 0.00 AC: 0 AN: 37908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23054

East Asian (EAS) AF: 0.00161 AC: 60 AN: 37378

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4778

European-Non Finnish (NFE) AF: 0.0000119 AC: 12 AN: 1012154

Other (OTH) AF: 0.00134 AC: 74 AN: 55158

GnomAD4 genome AF: 0.000206 AC: 24 AN: 116426 Hom.: 0 Cov.: 17 AF XY: 0.000201 AC XY: 11 AN XY: 54618

African (AFR) AF: 0.000226 AC: 8 AN: 35398

American (AMR) AF: 0.000187 AC: 2 AN: 10702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.00269 AC: 11 AN: 4082

South Asian (SAS) AF: 0.00 AC: 0 AN: 3460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51898

Other (OTH) AF: 0.00196 AC: 3 AN: 1530

Alfa AF: 0.000240 Hom.: 0

ExAC AF: 0.000168 AC: 19

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.052
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.012	T
MetaSVM	Uncertain	0.045	D
MutationAssessor	Benign	0.47	N
PhyloP100		1.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.084
MutPred		0.30		Gain of catalytic residue at T169 (P = 0.0016)
MVP		0.72
ClinPred		0.011	T
GERP RS		2.8
Varity_R		0.029
gMVP		0.12
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs536592072; hg19: chr13-24895410;