10-16520999-C-T

Position:

• chr10-16520999-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001010908.2(C1QL3):​c.67G>A​(p.Glu23Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,444,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: C1QL3 NM_001010908.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QL3	NM_001010908.2	c.67G>A	p.Glu23Lys	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.67G>A	p.Glu23Lys	missense_variant	1/2	1	NM_001010908.2	ENSP00000298943.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1444798 Hom.: 0 Cov.: 34 AF XY: 0.00000278 AC XY: 2 AN XY: 718616

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000835 AC: 1

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

May 01, 2022

The c.67G>A (p.E23K) 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 67, causing the glutamic acid (E) at amino acid position 23 to be replaced by a lysine (K). 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	0.84
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.73	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.2	N;.
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.016	D;D
Polyphen		1.0	D;.
Vest4		0.40
MutPred		0.58		Gain of ubiquitination at E23 (P = 0.0192);Gain of ubiquitination at E23 (P = 0.0192);
MVP		0.96
MPC		1.4
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.45
gMVP		0.64

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

Other links and lift over

dbSNP: rs613731; hg19: chr10-16562998;