Variant 9-137168984-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001013653.3(LRRC26):c.875C>A(p.Ala292Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000774 in 1,291,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

LRRC26
NM_001013653.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

LRRC26 (HGNC:31409): (leucine rich repeat containing 26) Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Is integral component of plasma membrane. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LRRC26 links:

ENSG00000261793 (HGNC:):

ENSG00000261793 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32621783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC26	NM_001013653.3 linkuse as main transcript	c.875C>A	p.Ala292Glu	missense_variant	2/2	ENST00000371542.3	NP_001013675.1	Q2I0M4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC26	ENST00000371542.3 linkuse as main transcript	c.875C>A	p.Ala292Glu	missense_variant	2/2	1	NM_001013653.3	ENSP00000360597.3		Q2I0M4-1
ENSG00000261793	ENST00000568665.1 linkuse as main transcript	c.*229C>A		3_prime_UTR_variant	3/3	3		ENSP00000480768.1		A0A087WX66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.74e-7

AC:

AN:

1291298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

635930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000356

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.875C>A (p.A292E) alteration is located in exon 2 (coding exon 2) of the LRRC26 gene. This alteration results from a C to A substitution at nucleotide position 875, causing the alanine (A) at amino acid position 292 to be replaced by a glutamic acid (E). 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

Benign

0.18

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.011

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.87

REVEL

Benign

0.24

Sift

Benign

0.30

Sift4G

Benign

0.076

Polyphen

0.96

Vest4

0.23

MutPred

0.42

Gain of solvent accessibility (P = 0.0411);

MVP

0.31

MPC

0.64

ClinPred

0.25

GERP RS

3.0

Varity_R

0.12

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over