Variant 13-24316163-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178540.5(C1QTNF9):c.160G>A(p.Asp54Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000294 in 1,598,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

C1QTNF9
NM_178540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

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 links:

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

C1QTNF9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22762394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF9	NM_178540.5 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	2/4	ENST00000332018.5
C1QTNF9	NM_001303137.2 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	3/5
C1QTNF9	NM_001303138.2 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C1QTNF9	ENST00000332018.5 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	2/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1 linkuse as main transcript	n.74-42C>T		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	2/4	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000398

AC:

AN:

150912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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

GnomAD3 exomes

AF:

0.0000453

AC:

AN:

242892

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131164

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000240

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1447930

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

718978

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000341

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151030

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73714

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

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

Jan 31, 2023

The c.160G>A (p.D54N) alteration is located in exon 2 (coding exon 1) of the C1QTNF9 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the aspartic acid (D) at amino acid position 54 to be replaced by an asparagine (N). 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

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.18

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.51

P;P

Vest4

0.26

MutPred

0.36

Gain of catalytic residue at K52 (P = 0.003);Gain of catalytic residue at K52 (P = 0.003);

MVP

0.88

ClinPred

0.068

GERP RS

3.9

Varity_R

0.21

gMVP

0.18

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

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