7-102934078-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001031692.3(LRRC17):​c.165C>G​(p.Asp55Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LRRC17
NM_001031692.3 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.420
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.085134).
BP6
Variant 7-102934078-C-G is Benign according to our data. Variant chr7-102934078-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3868334.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC17NM_001031692.3 linkc.165C>G p.Asp55Glu missense_variant Exon 2 of 4 ENST00000339431.9 NP_001026862.1 Q8N6Y2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC17ENST00000339431.9 linkc.165C>G p.Asp55Glu missense_variant Exon 2 of 4 1 NM_001031692.3 ENSP00000344242.4 Q8N6Y2-1
FBXL13ENST00000440067.4 linkc.995-2145G>C intron_variant Intron 9 of 20 3 ENSP00000390126.2 C9JI88

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 21, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
0.081
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
3.9
DANN
Benign
0.88
DEOGEN2
Benign
0.0022
T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.085
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.60
N;N;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.20
N;N;N
REVEL
Benign
0.096
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.035
MutPred
0.44
Loss of phosphorylation at Y57 (P = 0.0918);Loss of phosphorylation at Y57 (P = 0.0918);Loss of phosphorylation at Y57 (P = 0.0918);
MVP
0.47
MPC
0.24
ClinPred
0.032
T
GERP RS
-10
Varity_R
0.023
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102574525; API