rs201500795

Variant names:

• chr14-24427853-C-A
• rs201500795
• NM_001039771.3:c.554G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-24427853-C-A
• chr14-24427853-C-G
• chr14-24427853-C-T

Variant summary

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

The NM_001039771.3(CBLN3):​c.554G>T​(p.Arg185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CBLN3 NM_001039771.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

Genes affected

CBLN3 (HGNC:20146): (cerebellin 3 precursor) Members of the precerebellin family, such as CBLN3, contain a cerebellin motif (see CBLN1; MIM 600432) and a C-terminal C1q signature domain (see MIM 120550) that mediates trimeric assembly of atypical collagen complexes. However, precerebellins do not contain a collagen motif, suggesting that they are not conventional components of the extracellular matrix (Pang et al., 2000 [PubMed 10964938]).[supplied by OMIM, Aug 2009]

KHNYN (HGNC:20166): (KH and NYN domain containing) The protein encoded by this gene contains a ribonuclease NYN domain and belongs to the N4BP1 family. The protein is a cofactor for the zinc finger antiviral protein (ZAP protein) which targets viral RNA for degradation and restricts SARS-CoV-2 infection. [provided by RefSeq, Sep 2021]

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 rank	MANE	Protein	UniProt
CBLN3	NM_001039771.3	c.554G>T	p.Arg185Leu	missense_variant	Exon 3 of 3	ENST00000267406.11	NP_001034860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLN3	ENST00000267406.11	c.554G>T	p.Arg185Leu	missense_variant	Exon 3 of 3	1	NM_001039771.3	ENSP00000267406.6
CBLN3	ENST00000555436.1	c.401G>T	p.Arg134Leu	missense_variant	Exon 3 of 3	3		ENSP00000450935.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.029	D;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.50		Loss of methylation at R185 (P = 0.0189);.;
MVP		0.88
MPC		1.2
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.43
gMVP		0.70

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: rs201500795; hg19: chr14-24897059;