11-57182193-C-G

Variant names:

• chr11-57182193-C-G
• NM_001005210.4:c.171C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005210.4(LRRC55):​c.171C>G​(p.Phe57Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC55 NM_001005210.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1735762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC55	NM_001005210.4	c.171C>G	p.Phe57Leu	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.171C>G	p.Phe57Leu	missense_variant	Exon 1 of 2	1	NM_001005210.4	ENSP00000419542.2
LRRC55	ENST00000652194.1	c.300C>G	p.Phe100Leu	missense_variant	Exon 1 of 2			ENSP00000498533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.300C>G (p.F100L) alteration is located in exon 1 (coding exon 1) of the LRRC55 gene. This alteration results from a C to G substitution at nucleotide position 300, causing the phenylalanine (F) at amino acid position 100 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.056
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	0.11	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.53	N
REVEL	Uncertain	0.36
Sift	Benign	0.96	T
Sift4G	Benign	0.67	T
Vest4		0.18
MVP		0.72
MPC		0.48
ClinPred		0.88	D
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-56949667;