10-16520785-C-T

Position:

• chr10-16520785-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001010908.2(C1QL3):​c.281G>A​(p.Gly94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: C1QL3 NM_001010908.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QL3	NM_001010908.2	c.281G>A	p.Gly94Asp	missense_variant	1/2	ENST00000298943.4	NP_001010908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QL3	ENST00000298943.4	c.281G>A	p.Gly94Asp	missense_variant	1/2	1	NM_001010908.2	ENSP00000298943.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2023

The c.281G>A (p.G94D) alteration is located in exon 1 (coding exon 1) of the C1QL3 gene. This alteration results from a G to A substitution at nucleotide position 281, causing the glycine (G) at amino acid position 94 to be replaced by an aspartic acid (D). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.4	H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.84
MutPred		0.79		Gain of relative solvent accessibility (P = 0.005);
MVP		0.96
MPC		1.6
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.86
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-16562784;