dbSNP rs3751353: C1QTNF9:p.Gly77Ala (chr13-24320996-G-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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:

PCOTHP1 (HGNC:39840):

PCOTHP1 links:

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

C1QTNF9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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 rank	MANE	Protein	UniProt
C1QTNF9	NM_178540.5 link	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	Exon 4 of 4	ENST00000332018.5	NP_848635.2	P0C862A0A3B0J259
C1QTNF9	NM_001303137.2 link	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	Exon 5 of 5		NP_001290066.1	P0C862A0A3B0J259
C1QTNF9	NM_001303138.2 link	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	Exon 4 of 4		NP_001290067.1	P0C862A0A3B0J259
PCOTHP1		n.24320996G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C1QTNF9	ENST00000332018.5 link	c.230G>C	p.Gly77Ala	missense_variant, splice_region_variant	Exon 4 of 4	1	NM_178540.5	ENSP00000333737.4	P0C862
ENSG00000273167	ENST00000382141.4 link	n.*226G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 16 of 16	5		ENSP00000371576.4	A0A0A0MRY4
ENSG00000273167	ENST00000382141.4 link	n.*226G>C		3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000371576.4	A0A0A0MRY4

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

GnomAD2 exomes

AF:

0.00915

AC:

2104

AN:

229946

AF XY:

0.00710

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 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

African (AFR)

AF:

0.000403

AC:

AN:

32254

American (AMR)

AF:

0.0577

AC:

2201

AN:

38160

Ashkenazi Jewish (ASJ)

AF:

0.000328

AC:

AN:

24358

East Asian (EAS)

AF:

0.0287

AC:

1137

AN:

39646

South Asian (SAS)

AF:

0.000196

AC:

AN:

81664

European-Finnish (FIN)

AF:

0.0000949

AC:

AN:

52710

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.000107

AC:

118

AN:

1102968

Other (OTH)

AF:

0.00139

AC:

AN:

59186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00277

AC:

413

AN:

149078

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

211

AN XY:

72496

show subpopulations

African (AFR)

AF:

0.000615

AC:

AN:

40674

American (AMR)

AF:

0.0198

AC:

294

AN:

14834

Ashkenazi Jewish (ASJ)

AF:

0.000873

AC:

AN:

3438

East Asian (EAS)

AF:

0.0143

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000164

AC:

AN:

67272

Other (OTH)

AF:

0.00346

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.598

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

PhyloP100

8.7

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

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over