Variant 13-24321356-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_178540.5(C1QTNF9):c.590T>C(p.Leu197Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C1QTNF9
NM_178540.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05717373).

BP6

Variant 13-24321356-T-C is Benign according to our data. Variant chr13-24321356-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2554427.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C1QTNF9	NM_178540.5 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	4/4	ENST00000332018.5
C1QTNF9	NM_001303137.2 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	5/5
C1QTNF9	NM_001303138.2 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C1QTNF9	ENST00000332018.5 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	4/4	1	NM_178540.5	P1
C1QTNF9-AS1	ENST00000449656.1 linkuse as main transcript	n.73+170A>G		intron_variant, non_coding_transcript_variant		5
C1QTNF9	ENST00000382071.6 linkuse as main transcript	c.590T>C	p.Leu197Pro	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000412

AC:

AN:

1457524

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.0

DANN

Benign

0.65

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0062

M_CAP

Benign

0.0052

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-1.6

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.40

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;B

Vest4

0.044

MutPred

0.47

Gain of catalytic residue at K192 (P = 0.0013);Gain of catalytic residue at K192 (P = 0.0013);

MVP

0.51

ClinPred

0.033

GERP RS

3.1

Varity_R

0.063

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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