7-102934523-C-T

Variant names:

• chr7-102934523-C-T
• rs149650054
• NM_001031692.3:c.610C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001031692.3(LRRC17):​c.610C>T​(p.Arg204Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 1,607,940 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: LRRC17 NM_001031692.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1462462).

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.610C>T	p.Arg204Trp	missense	Exon 2 of 4	NP_001026862.1	Q8N6Y2-1
	FBXL13	NM_001394494.2	MANE Select	c.995-2590G>A		intron	N/A	NP_001381423.1	C9JI88
	LRRC17	NM_005824.3		c.610C>T	p.Arg204Trp	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.610C>T	p.Arg204Trp	missense	Exon 2 of 4	ENSP00000344242.4	Q8N6Y2-1
	LRRC17	ENST00000249377.4	TSL:1	c.610C>T	p.Arg204Trp	missense	Exon 2 of 5	ENSP00000249377.4	Q8N6Y2-2
	FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.995-2590G>A		intron	N/A	ENSP00000390126.2	C9JI88

Frequencies

GnomAD3 genomes AF: 0.0000411 AC: 6 AN: 146104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000587

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000301

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 249480 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00110

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1461714 Hom.: 0 Cov.: 33 AF XY: 0.0000344 AC XY: 25 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26130

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53402

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

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111946

Other (OTH) AF: 0.0000331 AC: 2 AN: 60382

GnomAD4 genome AF: 0.0000410 AC: 6 AN: 146226 Hom.: 0 Cov.: 32 AF XY: 0.0000422 AC XY: 3 AN XY: 71022

African (AFR) AF: 0.00 AC: 0 AN: 39896

American (AMR) AF: 0.00 AC: 0 AN: 14028

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3396

East Asian (EAS) AF: 0.000588 AC: 3 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66380

Other (OTH) AF: 0.00 AC: 0 AN: 1950

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000124 AC: 15

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	0.25
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.34
MutPred		0.36		Gain of ubiquitination at K201 (P = 0.0354)
MVP		0.79
MPC		0.47
ClinPred		0.17	T
GERP RS		3.1
Varity_R		0.095
gMVP		0.50
Mutation Taster		=84/16	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: rs149650054; hg19: chr7-102574970;