Variant chr1-3784109-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000378251.3(LRRC47):c.1197T>G(p.Ile399Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,608,240 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

LRRC47
ENST00000378251.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.494

Variant links:

Genes affected

LRRC47 (HGNC:29207): (leucine rich repeat containing 47) Enables RNA binding activity. Predicted to be involved in phenylalanyl-tRNA aminoacylation. [provided by Alliance of Genome Resources, Apr 2022]

LRRC47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
LRRC47	NM_020710.3 linkuse as main transcript	c.1197T>G	p.Ile399Met	missense_variant, splice_region_variant	4/7	ENST00000378251.3	NP_065761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC47	ENST00000378251.3 linkuse as main transcript	c.1197T>G	p.Ile399Met	missense_variant, splice_region_variant	4/7	1	NM_020710.3	ENSP00000367498	P1
LRRC47	ENST00000462356.5 linkuse as main transcript	n.67T>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000754

AC:

AN:

238620

Hom.:

AF XY:

0.0000850

AC XY:

AN XY:

129392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000556

AC:

AN:

1456034

Hom.:

Cov.:

AF XY:

0.0000691

AC XY:

AN XY:

723926

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000598

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2023

The c.1197T>G (p.I399M) alteration is located in exon 4 (coding exon 4) of the LRRC47 gene. This alteration results from a T to G substitution at nucleotide position 1197, causing the isoleucine (I) at amino acid position 399 to be replaced by a methionine (M). 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

Benign

0.28

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.62

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.71

MutPred

0.60

Loss of catalytic residue at P401 (P = 0.0303);

MVP

0.21

MPC

0.98

ClinPred

0.26

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.41

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

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