1-13513332-T-C

Position:

• chr1-13513332-T-C

Variant summary

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

The NM_001010847.2(LRRC38):​c.262A>G​(p.Arg88Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: LRRC38 NM_001010847.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

Genes affected

LRRC38 (HGNC:27005): (leucine rich repeat containing 38) Enables potassium channel activator activity and transmembrane transporter binding activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259961 (HGNC:):

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=0.20987552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC38	NM_001010847.2	c.262A>G	p.Arg88Gly	missense_variant	1/2	ENST00000376085.4	NP_001010847.1
LRRC38	XM_047444690.1	c.262A>G	p.Arg88Gly	missense_variant	1/2		XP_047300646.1
LOC107984918	XR_001737896.2	n.113T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC38	ENST00000376085.4	c.262A>G	p.Arg88Gly	missense_variant	1/2	1	NM_001010847.2	ENSP00000365253.3
ENSG00000259961	ENST00000563570.1	n.113T>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

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

Apr 21, 2022

The c.262A>G (p.R88G) alteration is located in exon 1 (coding exon 1) of the LRRC38 gene. This alteration results from a A to G substitution at nucleotide position 262, causing the arginine (R) at amino acid position 88 to be replaced by a glycine (G). 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	0.55
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.060
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.074	T
Polyphen		0.12	B
Vest4		0.38
MutPred		0.46		Loss of stability (P = 0.0104);
MVP		0.47
ClinPred		0.85	D
GERP RS		3.0
Varity_R		0.35
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1006281427; hg19: chr1-13839827;