chr7-102934071-C-T

Variant names:

• chr7-102934071-C-T
• rs750849321
• NM_001031692.3:c.158C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031692.3(LRRC17):​c.158C>T​(p.Pro53Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,850 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: LRRC17 NM_001031692.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26056284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031692.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC17	NM_001031692.3	MANE Select	c.158C>T	p.Pro53Leu	missense	Exon 2 of 4	NP_001026862.1	Q8N6Y2-1
	FBXL13	NM_001394494.2	MANE Select	c.995-2138G>A		intron	N/A	NP_001381423.1	C9JI88
	LRRC17	NM_005824.3		c.158C>T	p.Pro53Leu	missense	Exon 2 of 5	NP_005815.2	Q8N6Y2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC17	ENST00000339431.9	TSL:1 MANE Select	c.158C>T	p.Pro53Leu	missense	Exon 2 of 4	ENSP00000344242.4	Q8N6Y2-1
	LRRC17	ENST00000249377.4	TSL:1	c.158C>T	p.Pro53Leu	missense	Exon 2 of 5	ENSP00000249377.4	Q8N6Y2-2
	FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.995-2138G>A		intron	N/A	ENSP00000390126.2	C9JI88

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251148 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461850 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0077	T
Eigen	Benign	0.055
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.19
Sift	Uncertain	0.013	D
Sift4G	Benign	0.093	T
Polyphen		0.10	B
Vest4		0.57
MutPred		0.51		Loss of catalytic residue at P53 (P = 0.0482)
MVP		0.84
MPC		0.26
ClinPred		0.16	T
GERP RS		5.7
Varity_R		0.065
gMVP		0.53
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs750849321; hg19: chr7-102574518; COSMIC: COSV50864266; COSMIC: COSV50864266;