7-102933983-G-T

Position:

• chr7-102933983-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000339431.9(LRRC17):​c.70G>T​(p.Gly24Cys) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC17 ENST00000339431.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18136665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC17	NM_001031692.3	c.70G>T	p.Gly24Cys	missense_variant	2/4	ENST00000339431.9	NP_001026862.1
FBXL13	NM_001394494.2	c.995-2050C>A		intron_variant		ENST00000440067.4	NP_001381423.1
FBXL13	NR_105043.2	n.1021-2050C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC17	ENST00000339431.9	c.70G>T	p.Gly24Cys	missense_variant	2/4	1	NM_001031692.3	ENSP00000344242	P1
FBXL13	ENST00000440067.4	c.995-2050C>A		intron_variant		3	NM_001394494.2	ENSP00000390126	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.70G>T (p.G24C) alteration is located in exon 2 (coding exon 1) of the LRRC17 gene. This alteration results from a G to T substitution at nucleotide position 70, causing the glycine (G) at amino acid position 24 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0092	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	0.99	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.83	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.97	D;D;.
Vest4		0.35
MutPred		0.37		Gain of catalytic residue at P23 (P = 0.0086);Gain of catalytic residue at P23 (P = 0.0086);Gain of catalytic residue at P23 (P = 0.0086);
MVP		0.71
MPC		0.52
ClinPred		0.26	T
GERP RS		1.9
Varity_R		0.095
gMVP		0.46

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: chr7-102574430;