Variant 13-23891759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001007537.3(C1QTNF9B):c.532C>T(p.Arg178Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000526 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C1QTNF9B
NM_001007537.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

C1QTNF9B (HGNC:34072): (C1q and TNF related 9B) Predicted to enable hormone activity and identical protein binding activity. Predicted to act upstream of or within several processes, including energy homeostasis; negative regulation of cell size; and positive regulation of protein serine/threonine kinase activity. Predicted to be located in extracellular space. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF9B links:

PCOTH (HGNC:39839): (prostate and testis expressed opposite C1QTNF9B and MIPEP) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PCOTH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
C1QTNF9B	NM_001007537.3 link	c.532C>T	p.Arg178Trp	missense_variant	5/5	NP_001007538.1	B2RNN3-1
C1QTNF9B	XM_047430301.1 link	c.289-248C>T		intron_variant		XP_047286257.1
PCOTH	NR_172510.1 link	n.481G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
C1QTNF9B	ENST00000382137.7 link	c.532C>T	p.Arg178Trp	missense_variant	3/3	1	ENSP00000371572.3	B2RNN3-1
C1QTNF9B	ENST00000382145.5 link	c.266-248C>T		intron_variant		1	ENSP00000371580.1	A0A0C4DFX8
PCOTH	ENST00000382133.9 link	n.507G>A		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250596

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000274

AC:

AN:

1461632

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.532C>T (p.R178W) alteration is located in exon 3 (coding exon 3) of the C1QTNF9B gene. This alteration results from a C to T substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a tryptophan (W). 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

Uncertain

0.014

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.078

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D

M_CAP

Pathogenic

0.43

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.68

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.90

MPC

1.9

ClinPred

0.88

GERP RS

2.4

Varity_R

0.41

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over