chr3-120335057-C-T

Variant names:

• chr3-120335057-C-T
• NM_001099678.2:c.712G>A

Variant summary

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

The NM_001099678.2(LRRC58):​c.712G>A​(p.Glu238Lys) 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. 13/21 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: LRRC58 NM_001099678.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

Genes affected

LRRC58 (HGNC:26968): (leucine rich repeat containing 58)

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=0.15995899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC58	NM_001099678.2	c.712G>A	p.Glu238Lys	missense_variant	Exon 3 of 4	ENST00000295628.4	NP_001093148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC58	ENST00000295628.4	c.712G>A	p.Glu238Lys	missense_variant	Exon 3 of 4	1	NM_001099678.2	ENSP00000295628.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.712G>A (p.E238K) alteration is located in exon 3 (coding exon 3) of the LRRC58 gene. This alteration results from a G to A substitution at nucleotide position 712, causing the glutamic acid (E) at amino acid position 238 to be replaced by a lysine (K). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.043
Sift	Benign	0.30	T
Sift4G	Benign	0.85	T
Polyphen		0.020	B
Vest4		0.38
MutPred		0.40		Loss of catalytic residue at E238 (P = 0.0268);
MVP		0.36
MPC		1.0
ClinPred		0.42	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-120053904;