11-57182267-C-T

Variant names:

• chr11-57182267-C-T
• rs748897052
• NM_001005210.4:c.245C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001005210.4(LRRC55):​c.245C>T​(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: LRRC55 NM_001005210.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

Genes affected

LRRC55 (HGNC:32324): (leucine rich repeat containing 55) 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. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC105369309 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.086286455).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC55	NM_001005210.4	c.245C>T	p.Pro82Leu	missense_variant	Exon 1 of 2	ENST00000497933.3	NP_001005210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC55	ENST00000497933.3	c.245C>T	p.Pro82Leu	missense_variant	Exon 1 of 2	1	NM_001005210.4	ENSP00000419542.2
LRRC55	ENST00000652194.1	c.374C>T	p.Pro125Leu	missense_variant	Exon 1 of 2			ENSP00000498533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000278 AC: 7 AN: 251350 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.374C>T (p.P125L) alteration is located in exon 1 (coding exon 1) of the LRRC55 gene. This alteration results from a C to T substitution at nucleotide position 374, causing the proline (P) at amino acid position 125 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.046
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.14
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Vest4		0.15
MVP		0.12
MPC		0.085
ClinPred		0.15	T
GERP RS		5.8

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

Other links and lift over

dbSNP: rs748897052; hg19: chr11-56949741;