rs769454429

Variant names:

• chr7-102934052-C-A
• NM_001031692.3:c.139C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-102934052-C-A
• chr7-102934052-C-T

Variant summary

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

The NM_001031692.3(LRRC17):​c.139C>A​(p.Arg47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC17 NM_001031692.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC17	NM_001031692.3	c.139C>A	p.Arg47Ser	missense_variant	Exon 2 of 4	ENST00000339431.9	NP_001026862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC17	ENST00000339431.9	c.139C>A	p.Arg47Ser	missense_variant	Exon 2 of 4	1	NM_001031692.3	ENSP00000344242.4
FBXL13	ENST00000440067.4	c.995-2119G>T		intron_variant	Intron 9 of 20	3		ENSP00000390126.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461810 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.34	N;N;D
REVEL	Uncertain	0.33
Sift	Benign	0.12	T;T;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.84
MutPred		0.44		Gain of ubiquitination at K46 (P = 0.0204);Gain of ubiquitination at K46 (P = 0.0204);Gain of ubiquitination at K46 (P = 0.0204);
MVP		0.88
MPC		0.95
ClinPred		0.80	D
GERP RS		4.7
Varity_R		0.27
gMVP		0.53

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: chr7-102574499;