Variant chr10-127883725-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152311.5(CLRN3):c.380C>T(p.Thr127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000733 in 1,613,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

CLRN3
NM_152311.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

Variant links:

Genes affected

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

CLRN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02380389).

BP6

Variant 10-127883725-G-A is Benign according to our data. Variant chr10-127883725-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2281259.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLRN3	NM_152311.5 linkuse as main transcript	c.380C>T	p.Thr127Met	missense_variant	2/3	ENST00000368671.4
CLRN3	XM_011539274.3 linkuse as main transcript	c.230-5305C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLRN3	ENST00000368671.4 linkuse as main transcript	c.380C>T	p.Thr127Met	missense_variant	2/3	1	NM_152311.5	P1	Q8NCR9-1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000625

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251448

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000747

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000759

AC:

1110

AN:

1461566

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

553

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000942

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000480

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000670

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.041

DANN

Benign

0.89

DEOGEN2

Benign

0.00067

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.27

M_CAP

Benign

0.056

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

0.43

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.18

Polyphen

0.0040

Vest4

0.18

MVP

0.33

MPC

0.054

ClinPred

0.032

GERP RS

-6.1

Varity_R

0.018

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over