NM_001013653.3:c.641C>T

Variant names:

Variant summary

Our verdict is . The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001013653.3(LRRC26):c.641C>T(p.Ala214Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000847 in 1,416,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A214G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

LRRC26
NM_001013653.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.658

Publications

0 publications found

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:

MIR3621 (HGNC:38930): (microRNA 3621) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3621 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001013653.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.044).

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013653.3. 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
	LRRC26	NM_001013653.3	MANE Select	c.641C>T	p.Ala214Val	missense	Exon 1 of 2	NP_001013675.1	Q2I0M4-1
	MIR3621	NR_037416.1		n.-33C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC26	ENST00000371542.3	TSL:1 MANE Select	c.641C>T	p.Ala214Val	missense	Exon 1 of 2	ENSP00000360597.3	Q2I0M4-1
ENSG00000261793	ENST00000568665.1	TSL:3	c.*28-118C>T		intron	N/A	ENSP00000480768.1	A0A087WX66
MIR3621	ENST00000580529.1	TSL:6	n.-33C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

41824

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000313

Gnomad NFE exome

AF:

0.0000604

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000475

AC:

AN:

1264130

Hom.:

Cov.:

AF XY:

0.00000483

AC XY:

AN XY:

620556

show subpopulations

African (AFR)

AF:

0.0000404

AC:

AN:

24726

American (AMR)

AF:

0.00

AC:

AN:

15888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20442

East Asian (EAS)

AF:

0.00

AC:

AN:

27536

South Asian (SAS)

AF:

0.00

AC:

AN:

63446

European-Finnish (FIN)

AF:

0.0000951

AC:

AN:

31538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3812

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1024670

Other (OTH)

AF:

0.00

AC:

AN:

52072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.021

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.40

M_CAP

Benign

0.028

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PhyloP100

-0.66

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.1

REVEL

Benign

0.044

Sift

Benign

0.28

Sift4G

Benign

0.33

Varity_R

0.044

gMVP

0.21

Mutation Taster

=93/7

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over