10-127878271-C-G

Variant names:

• chr10-127878271-C-G
• rs768006534
• NM_152311.5:c.559G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152311.5(CLRN3):​c.559G>C​(p.Val187Leu) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V187I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLRN3 NM_152311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

Genes affected

CLRN3 (HGNC:20795): (clarin 3) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067687005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152311.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN3	NM_152311.5	MANE Select	c.559G>C	p.Val187Leu	missense	Exon 3 of 3	NP_689524.1	Q8NCR9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN3	ENST00000368671.4	TSL:1 MANE Select	c.559G>C	p.Val187Leu	missense	Exon 3 of 3	ENSP00000357660.3	Q8NCR9-1
	CLRN3	ENST00000856090.1		c.571G>C	p.Val191Leu	missense	Exon 3 of 3	ENSP00000526149.1
	CLRN3	ENST00000856089.1		c.556G>C	p.Val186Leu	missense	Exon 3 of 3	ENSP00000526148.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.69
DANN	Benign	0.68
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.21	T
Sift4G	Benign	0.087	T
Polyphen		0.019	B
Vest4		0.20
MutPred		0.37		Gain of helix (P = 0.1736)
MVP		0.20
MPC		0.075
ClinPred		0.081	T
GERP RS		-1.9
Varity_R		0.046
gMVP		0.54
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768006534; hg19: chr10-129676535;