11-57182338-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001005210.4(LRRC55):​c.316C>T​(p.Arg106Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LRRC55
NM_001005210.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.209
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09428042).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC55NM_001005210.4 linkc.316C>T p.Arg106Trp missense_variant Exon 1 of 2 ENST00000497933.3 NP_001005210.2 Q6ZSA7A0A494C0H1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC55ENST00000497933.3 linkc.316C>T p.Arg106Trp missense_variant Exon 1 of 2 1 NM_001005210.4 ENSP00000419542.2 Q6ZSA7
LRRC55ENST00000652194.1 linkc.445C>T p.Arg149Trp missense_variant Exon 1 of 2 ENSP00000498533.1 A0A494C0H1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250022
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135226
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461540
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727068
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 28, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.445C>T (p.R149W) 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 445, causing the arginine (R) at amino acid position 149 to be replaced by a tryptophan (W). 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
-0.45
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
22
DANN
Uncertain
0.99
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.078
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-0.96
T
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.065
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.18
T
Vest4
0.30
MVP
0.17
MPC
0.088
ClinPred
0.14
T
GERP RS
-0.97

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.

Other links and lift over

dbSNP: rs754673684; hg19: chr11-56949812; COSMIC: COSV73007045; API