Genetic Variant C1QTNF9:p.Ala48Val (chr13-24316146-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178540.5(C1QTNF9):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000952 in 1,606,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

C1QTNF9
NM_178540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.500

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:

ENSG00000273167 (HGNC:):

ENSG00000273167 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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02434215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF9	NM_178540.5 link	c.143C>T	p.Ala48Val	missense_variant	Exon 2 of 4	ENST00000332018.5	NP_848635.2	P0C862A0A3B0J259
C1QTNF9	NM_001303137.2 link	c.143C>T	p.Ala48Val	missense_variant	Exon 3 of 5		NP_001290066.1	P0C862A0A3B0J259
C1QTNF9	NM_001303138.2 link	c.143C>T	p.Ala48Val	missense_variant	Exon 2 of 4		NP_001290067.1	P0C862A0A3B0J259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C1QTNF9	ENST00000332018.5 link	c.143C>T	p.Ala48Val	missense_variant	Exon 2 of 4	1	NM_178540.5	ENSP00000333737.4	P0C862
ENSG00000273167	ENST00000382141.4 link	n.*139C>T		non_coding_transcript_exon_variant	Exon 14 of 16	5		ENSP00000371576.4	A0A0A0MRY4
ENSG00000273167	ENST00000382141.4 link	n.*139C>T		3_prime_UTR_variant	Exon 14 of 16	5		ENSP00000371576.4	A0A0A0MRY4

Frequencies

GnomAD3 genomes

AF:

0.0000796

AC:

AN:

150686

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.000869

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000137

AC:

AN:

248144

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

134108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00186

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.0000968

AC:

141

AN:

1456034

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

723576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00209

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000677

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000796

AC:

AN:

150686

Hom.:

Cov.:

AF XY:

0.0000953

AC XY:

AN XY:

73466

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.000869

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000206

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143C>T (p.A48V) alteration is located in exon 2 (coding exon 1) of the C1QTNF9 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 to be replaced by a valine (V). 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

0.086

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.7

DANN

Benign

0.91

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.21

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.44

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.13

Sift

Benign

0.29

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0020

B;B

Vest4

0.13

MVP

0.70

ClinPred

0.041

GERP RS

3.0

Varity_R

0.056

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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