chr1-13513056-A-T

Variant names:

• chr1-13513056-A-T
• NM_001010847.2:c.538T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001010847.2(LRRC38):​c.538T>A​(p.Ser180Thr) 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. 16/22 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: 0.600
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069325715).
• BP6: Variant 1-13513056-A-T is Benign according to our data. Variant chr1-13513056-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2534254.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC38	NM_001010847.2	c.538T>A	p.Ser180Thr	missense_variant	Exon 1 of 2	ENST00000376085.4	NP_001010847.1
LRRC38	XM_047444690.1	c.538T>A	p.Ser180Thr	missense_variant	Exon 1 of 2		XP_047300646.1
LOC107984918	XR_001737896.2	n.-164A>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC38	ENST00000376085.4	c.538T>A	p.Ser180Thr	missense_variant	Exon 1 of 2	1	NM_001010847.2	ENSP00000365253.3
ENSG00000259961	ENST00000563570.1	n.-164A>T		upstream_gene_variant		3

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

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.067
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.3
DANN	Benign	0.77
DEOGEN2	Benign	0.00075	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		0.60
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.048
MutPred		0.33		Loss of helix (P = 0.1706);
MVP		0.095
ClinPred		0.045	T
GERP RS		2.0
Varity_R		0.039
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr1-13839551;