NM_181506.5:c.155C>T

Variant summary

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

The NM_181506.5(LRRC70):​c.155C>T​(p.Ser52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000774 in 1,550,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

LRRC70
NM_181506.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
LRRC70 (HGNC:35155): (leucine rich repeat containing 70) Involved in positive regulation of response to cytokine stimulus. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

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=0.16536397).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC70NM_181506.5 linkc.155C>T p.Ser52Leu missense_variant Exon 2 of 2 ENST00000334994.6 NP_852607.3 Q7Z2Q7
IPO11NM_016338.5 linkc.2583-11984C>T intron_variant Intron 27 of 29 ENST00000325324.11 NP_057422.3 Q9UI26-1
IPO11NM_001134779.2 linkc.2703-11984C>T intron_variant Intron 27 of 29 NP_001128251.1 Q9UI26-2
IPO11-LRRC70NR_073584.1 linkn.201+658C>T intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC70ENST00000334994.6 linkc.155C>T p.Ser52Leu missense_variant Exon 2 of 2 1 NM_181506.5 ENSP00000399441.1 Q7Z2Q7
IPO11ENST00000325324.11 linkc.2583-11984C>T intron_variant Intron 27 of 29 1 NM_016338.5 ENSP00000316651.6 Q9UI26-1
IPO11ENST00000424533.5 linkn.*73+110C>T intron_variant Intron 28 of 28 2 ENSP00000395685.1 F8WDV0

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152008
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.0000195
AC:
3
AN:
153550
Hom.:
0
AF XY:
0.0000368
AC XY:
3
AN XY:
81462
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000811
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000439
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000715
AC:
10
AN:
1398888
Hom.:
0
Cov.:
32
AF XY:
0.0000116
AC XY:
8
AN XY:
689964
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152008
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000657
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:
0.0000282
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.155C>T (p.S52L) alteration is located in exon 2 (coding exon 1) of the LRRC70 gene. This alteration results from a C to T substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 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
0.10
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;.
Eigen
Benign
0.095
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.0
N;D
REVEL
Benign
0.077
Sift
Benign
0.39
T;D
Sift4G
Uncertain
0.015
D;D
Polyphen
0.96
D;.
Vest4
0.15
MutPred
0.41
Loss of disorder (P = 0.0405);Loss of disorder (P = 0.0405);
MVP
0.25
ClinPred
0.45
T
GERP RS
4.5
Varity_R
0.10
gMVP
0.33

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: rs1408227447; hg19: chr5-61875420; API