1-13513091-C-T

Position:

• chr1-13513091-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001010847.2(LRRC38):​c.503G>A​(p.Ser168Asn) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: LRRC38 NM_001010847.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053644717).
• BP6: Variant 1-13513091-C-T is Benign according to our data. Variant chr1-13513091-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2534252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC38	NM_001010847.2	c.503G>A	p.Ser168Asn	missense_variant	1/2	ENST00000376085.4	NP_001010847.1
LRRC38	XM_047444690.1	c.503G>A	p.Ser168Asn	missense_variant	1/2		XP_047300646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC38	ENST00000376085.4	c.503G>A	p.Ser168Asn	missense_variant	1/2	1	NM_001010847.2	ENSP00000365253	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.84
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.99	L
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.13
Sift	Benign	0.76	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.049
MutPred		0.48		Gain of catalytic residue at S168 (P = 0.0429);
MVP		0.088
ClinPred		0.030	T
GERP RS		0.20
Varity_R		0.045
gMVP		0.099

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: chr1-13839586;