Variant rs3751353 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BA1

The NM_178540.5(C1QTNF9):c.230G>C(p.Gly77Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,585,650 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0028 ( 11 hom., cov: 23)

Exomes 𝑓: 0.0025 ( 127 hom. )

Consequence

C1QTNF9
NM_178540.5 missense, splice_region

Scores

Splicing: ADA: 0.9962

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.70

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 Benign. Variant got -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: BayesDel_noAF, Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when AlphaMissense, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C1QTNF9	NM_178540.5 linkuse as main transcript	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	4/4	ENST00000332018.5	NP_848635.2
C1QTNF9	NM_001303137.2 linkuse as main transcript	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	5/5		NP_001290066.1
C1QTNF9	NM_001303138.2 linkuse as main transcript	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	4/4		NP_001290067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C1QTNF9	ENST00000332018.5 linkuse as main transcript	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	4/4	1	NM_178540.5	ENSP00000333737	P1
C1QTNF9-AS1	ENST00000449656.1 linkuse as main transcript	n.73+530C>G		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6 linkuse as main transcript	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	4/4	5		ENSP00000371503	P1

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

412

AN:

148968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000616

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.000873

Gnomad EAS

AF:

0.0142

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00350

GnomAD3 exomes

AF:

0.00915

AC:

2104

AN:

229946

Hom.:

AF XY:

0.00710

AC XY:

887

AN XY:

125016

show subpopulations

Gnomad AFR exome

AF:

0.000783

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.000356

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.000265

Gnomad FIN exome

AF:

0.0000949

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.00513

GnomAD4 exome

AF:

0.00249

AC:

3581

AN:

1436572

Hom.:

127

Cov.:

AF XY:

0.00217

AC XY:

1552

AN XY:

714418

show subpopulations

Gnomad4 AFR exome

AF:

0.000403

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.000328

Gnomad4 EAS exome

AF:

0.0287

Gnomad4 SAS exome

AF:

0.000196

Gnomad4 FIN exome

AF:

0.0000949

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00277

AC:

413

AN:

149078

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

211

AN XY:

72496

show subpopulations

Gnomad4 AFR

AF:

0.000615

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.000873

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000164

Gnomad4 OTH

AF:

0.00346

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00551

ESP6500AA

AF:

0.000913

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00734

AC:

891

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.73

D;D

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

.;D

MetaRNN

Benign

0.0077

T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

3.2

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0060

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.78

P;P

Vest4

0.63

MVP

0.92

ClinPred

0.086

GERP RS

4.1

Varity_R

0.89

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.96

SpliceAI score (max)

0.78

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.78

Position offset: 3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over