chr10-127883836-T-C

Position:

• chr10-127883836-T-C

Variant summary

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

The NM_152311.5(CLRN3):​c.269A>G​(p.His90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLRN3 NM_152311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.921

Genes affected

CLRN3 (HGNC:20795): (clarin 3) Located in extracellular exosome. [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	UniProt
CLRN3	NM_152311.5	c.269A>G	p.His90Arg	missense_variant	2/3	ENST00000368671.4
CLRN3	XM_011539274.3	c.230-5416A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLRN3	ENST00000368671.4	c.269A>G	p.His90Arg	missense_variant	2/3	1	NM_152311.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 07, 2022

The c.269A>G (p.H90R) alteration is located in exon 2 (coding exon 2) of the CLRN3 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the histidine (H) at amino acid position 90 to be replaced by an arginine (R). 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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.97	D
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.35
Sift	Benign	0.18	T
Sift4G	Uncertain	0.027	D
Polyphen		0.44	B
Vest4		0.57
MutPred		0.38		Loss of ubiquitination at K87 (P = 0.0391);
MVP		0.79
MPC		0.26
ClinPred		0.86	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.76

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: rs756403169; hg19: chr10-129682100;