chr9-137169282-A-C

Position:

• chr9-137169282-A-C

Variant summary

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

The NM_001013653.3(LRRC26):​c.662T>G​(p.Leu221Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: LRRC26 NM_001013653.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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]

ENSG00000261793 (HGNC:):

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=0.052239984).
• BP6: Variant 9-137169282-A-C is Benign according to our data. Variant chr9-137169282-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2261066.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC26	NM_001013653.3	c.662T>G	p.Leu221Arg	missense_variant	1/2	ENST00000371542.3	NP_001013675.1
MIR3621	NR_037416.1	n.-12T>G		upstream_gene_variant
MIR3621	unassigned_transcript_1708	n.-27T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC26	ENST00000371542.3	c.662T>G	p.Leu221Arg	missense_variant	1/2	1	NM_001013653.3	ENSP00000360597.3
ENSG00000261793	ENST00000568665.1	c.*28-97T>G		intron_variant		3		ENSP00000480768.1
MIR3621	ENST00000580529.1	n.-12T>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

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

Nov 15, 2021

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	0.058
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.58
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.97	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.012
Sift	Benign	0.68	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.063
MutPred		0.45		Gain of MoRF binding (P = 0.0239);
MVP		0.067
MPC		0.81
ClinPred		0.053	T
GERP RS		-3.5
Varity_R		0.045
gMVP		0.44

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: chr9-140063734;