chr3-120335057-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

Genes affected

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

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=0.15995899).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099678.2. 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
	LRRC58	NM_001099678.2	MANE Select	c.712G>A	p.Glu238Lys	missense	Exon 3 of 4	NP_001093148.1	Q96CX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC58	ENST00000295628.4	TSL:1 MANE Select	c.712G>A	p.Glu238Lys	missense	Exon 3 of 4	ENSP00000295628.3	Q96CX6
	LRRC58	ENST00000946153.1		c.712G>A	p.Glu238Lys	missense	Exon 3 of 4	ENSP00000616212.1
	LRRC58	ENST00000886041.1		c.583G>A	p.Glu195Lys	missense	Exon 2 of 3	ENSP00000556100.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	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
PhyloP100		3.4
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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

hg19: chr3-120053904; COSMIC: COSV107339658;