Variant 7-102944597-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000339431.9(LRRC17):c.1316T>A(p.Ile439Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000025 in 1,599,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC17
ENST00000339431.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

LRRC17 (HGNC:16895): (leucine rich repeat containing 17) Predicted to be involved in bone marrow development and negative regulation of osteoclast differentiation. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LRRC17 links:

FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXL13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35032713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC17	NM_001031692.3 linkuse as main transcript	c.1316T>A	p.Ile439Lys	missense_variant	4/4	ENST00000339431.9	NP_001026862.1
FBXL13	NM_001394494.2 linkuse as main transcript	c.995-12664A>T		intron_variant		ENST00000440067.4	NP_001381423.1
FBXL13	NR_105043.2 linkuse as main transcript	n.1021-12664A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC17	ENST00000339431.9 linkuse as main transcript	c.1316T>A	p.Ile439Lys	missense_variant	4/4	1	NM_001031692.3	ENSP00000344242	P1	Q8N6Y2-1
FBXL13	ENST00000440067.4 linkuse as main transcript	c.995-12664A>T		intron_variant		3	NM_001394494.2	ENSP00000390126	P2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447280

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719274

show subpopulations

Gnomad4 AFR exome

AF:

0.0000614

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Oct 12, 2021

The c.1316T>A (p.I439K) alteration is located in exon 4 (coding exon 3) of the LRRC17 gene. This alteration results from a T to A substitution at nucleotide position 1316, causing the isoleucine (I) at amino acid position 439 to be replaced by a lysine (K). 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

0.39

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.51

M_CAP

Benign

0.063

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.2

REVEL

Benign

0.15

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.39

MutPred

0.34

Gain of disorder (P = 0.0017);

MVP

0.67

MPC

0.93

ClinPred

0.79

GERP RS

6.0

Varity_R

0.27

gMVP

0.85

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

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