5-62579458-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181506.5(LRRC70):​c.20C>T​(p.Ser7Phe) 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. 16/20 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)

Consequence

LRRC70
NM_181506.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.521
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 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=0.09389922).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC70NM_181506.5 linkc.20C>T p.Ser7Phe missense_variant Exon 2 of 2 ENST00000334994.6 NP_852607.3 Q7Z2Q7
IPO11NM_016338.5 linkc.2583-12119C>T intron_variant Intron 27 of 29 ENST00000325324.11 NP_057422.3 Q9UI26-1
IPO11NM_001134779.2 linkc.2703-12119C>T intron_variant Intron 27 of 29 NP_001128251.1 Q9UI26-2
IPO11-LRRC70NR_073584.1 linkn.201+523C>T intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC70ENST00000334994.6 linkc.20C>T p.Ser7Phe missense_variant Exon 2 of 2 1 NM_181506.5 ENSP00000399441.1 Q7Z2Q7
IPO11ENST00000325324.11 linkc.2583-12119C>T intron_variant Intron 27 of 29 1 NM_016338.5 ENSP00000316651.6 Q9UI26-1
IPO11ENST00000424533.5 linkn.*48C>T non_coding_transcript_exon_variant Exon 28 of 29 2 ENSP00000395685.1 F8WDV0
IPO11ENST00000424533.5 linkn.*48C>T 3_prime_UTR_variant Exon 28 of 29 2 ENSP00000395685.1 F8WDV0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20C>T (p.S7F) 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 20, causing the serine (S) at amino acid position 7 to be replaced by a phenylalanine (F). 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
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
18
DANN
Benign
0.89
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.094
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.097
Sift
Benign
0.18
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.044
B;.
Vest4
0.29
MutPred
0.47
Loss of disorder (P = 0.0069);Loss of disorder (P = 0.0069);
MVP
0.18
ClinPred
0.15
T
GERP RS
4.3
Varity_R
0.054
gMVP
0.30

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: chr5-61875285; COSMIC: COSV100320335; COSMIC: COSV100320335; API