chr10-127883698-C-T

Variant names:

• chr10-127883698-C-T
• rs1030510108
• NM_152311.5:c.407G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152311.5(CLRN3):​c.407G>A​(p.Gly136Asp) variant causes a missense, splice region 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. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLRN3 NM_152311.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001103
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0550
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30343014).

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.407G>A	p.Gly136Asp	missense splice_region	Exon 2 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.407G>A	p.Gly136Asp	missense splice_region	Exon 2 of 3	ENSP00000357660.3	Q8NCR9-1
	CLRN3	ENST00000856090.1		c.407G>A	p.Gly136Asp	missense	Exon 2 of 3	ENSP00000526149.1
	CLRN3	ENST00000856091.1		c.401G>A	p.Gly134Asp	missense splice_region	Exon 2 of 3	ENSP00000526150.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.055
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.17
Sift	Benign	0.088	T
Sift4G	Benign	0.28	T
Polyphen		0.029	B
Vest4		0.57
MutPred		0.46		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.57
MPC		0.083
ClinPred		0.10	T
GERP RS		1.9
Varity_R		0.066
gMVP		0.79
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs1030510108; hg19: chr10-129681962;