Variant 10-16520773-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001010908.2(C1QL3):c.293G>C(p.Arg98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,304,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

C1QL3
NM_001010908.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.775

Variant links:

Genes affected

C1QL3 (HGNC:19359): (complement C1q like 3) Predicted to enable identical protein binding activity. Predicted to act upstream of or within regulation of synapse organization. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

C1QL3 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=0.09964234).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QL3	NM_001010908.2 linkuse as main transcript	c.293G>C	p.Arg98Pro	missense_variant	1/2	ENST00000298943.4	NP_001010908.1	Q5VWW1-1A0A3B0J0F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QL3	ENST00000298943.4 linkuse as main transcript	c.293G>C	p.Arg98Pro	missense_variant	1/2	1	NM_001010908.2	ENSP00000298943.3		Q5VWW1-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000192

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

119

AN:

1153670

Hom.:

Cov.:

AF XY:

0.0000972

AC XY:

AN XY:

555306

show subpopulations

Gnomad4 AFR exome

AF:

0.0000435

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000114

Gnomad4 FIN exome

AF:

0.0000265

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000112

AC:

AN:

151292

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73854

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ExAC

AF:

0.000155

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

Nov 15, 2024

The c.293G>C (p.R98P) alteration is located in exon 1 (coding exon 1) of the C1QL3 gene. This alteration results from a G to C substitution at nucleotide position 293, causing the arginine (R) at amino acid position 98 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.22

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.78

M_CAP

Benign

0.069

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.60

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

REVEL

Benign

0.026

Sift

Benign

0.45

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.15

MutPred

0.42

Loss of methylation at R98 (P = 0.035);

MVP

0.20

MPC

1.9

ClinPred

0.26

GERP RS

1.4

Varity_R

0.52

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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