7-102944411-A-C

Position:

• chr7-102944411-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000339431.9(LRRC17):​c.1130A>C​(p.Glu377Ala) variant causes a missense change. 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: 32)
• Consequence: LRRC17 ENST00000339431.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3024261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC17	NM_001031692.3	c.1130A>C	p.Glu377Ala	missense_variant	4/4	ENST00000339431.9	NP_001026862.1
FBXL13	NM_001394494.2	c.995-12478T>G		intron_variant		ENST00000440067.4	NP_001381423.1
FBXL13	NR_105043.2	n.1021-12478T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC17	ENST00000339431.9	c.1130A>C	p.Glu377Ala	missense_variant	4/4	1	NM_001031692.3	ENSP00000344242	P1
FBXL13	ENST00000440067.4	c.995-12478T>G		intron_variant		3	NM_001394494.2	ENSP00000390126	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 21, 2021

The c.1130A>C (p.E377A) alteration is located in exon 4 (coding exon 3) of the LRRC17 gene. This alteration results from a A to C substitution at nucleotide position 1130, causing the glutamic acid (E) at amino acid position 377 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0052	T
Eigen	Benign	0.068
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.075
Sift	Benign	0.35	T
Sift4G	Benign	0.40	T
Polyphen		0.43	B
Vest4		0.43
MutPred		0.40		Loss of disorder (P = 0.0607);
MVP		0.68
MPC		0.32
ClinPred		0.58	D
GERP RS		5.8
Varity_R		0.18
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: chr7-102584858;