10-127883704-C-T

Variant names:

• chr10-127883704-C-T
• NM_152311.5:c.401G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152311.5(CLRN3):​c.401G>A​(p.Gly134Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLRN3 NM_152311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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.401G>A	p.Gly134Glu	missense	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.401G>A	p.Gly134Glu	missense	Exon 2 of 3	ENSP00000357660.3	Q8NCR9-1
	CLRN3	ENST00000856090.1		c.401G>A	p.Gly134Glu	missense	Exon 2 of 3	ENSP00000526149.1
	CLRN3	ENST00000856089.1		c.401G>A	p.Gly134Glu	missense	Exon 2 of 3	ENSP00000526148.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460374 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726624

African (AFR) AF: 0.0000299 AC: 1 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110670

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.44		Loss of sheet (P = 0.0817)
MVP		0.87
MPC		0.38
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.70
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr10-129681968;