Variant 7-102939453-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031692.3(LRRC17):c.796A>T(p.Ile266Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000233 in 1,456,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LRRC17
NM_001031692.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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:

LRRC17 (HGNC:):

LRRC17 links:

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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
LRRC17	NM_001031692.3 linkuse as main transcript	c.796A>T	p.Ile266Phe	missense_variant	3/4	ENST00000339431.9	NP_001026862.1	Q8N6Y2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC17	ENST00000339431.9 linkuse as main transcript	c.796A>T	p.Ile266Phe	missense_variant	3/4	1	NM_001031692.3	ENSP00000344242.4		Q8N6Y2-1
FBXL13	ENST00000440067.4 linkuse as main transcript	c.995-7520T>A		intron_variant		3		ENSP00000390126.2		C9JI88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1456600

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724704

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

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

Jan 03, 2022

The c.796A>T (p.I266F) alteration is located in exon 3 (coding exon 2) of the LRRC17 gene. This alteration results from a A to T substitution at nucleotide position 796, causing the isoleucine (I) at amino acid position 266 to be replaced by a phenylalanine (F). 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

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

0.99

D;D

Vest4

0.55

MutPred

0.32

Loss of catalytic residue at P268 (P = 0.0447);Loss of catalytic residue at P268 (P = 0.0447);

MVP

0.75

MPC

1.0

ClinPred

0.99

GERP RS

6.0

Varity_R

0.50

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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