5-62579458-C-T

Variant names:

• chr5-62579458-C-T
• NM_181506.5:c.20C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.521
• Publications: 0 publications found

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]

IPO11-LRRC70 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09389922).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181506.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC70	NM_181506.5	MANE Select	c.20C>T	p.Ser7Phe	missense	Exon 2 of 2	NP_852607.3
	IPO11	NM_016338.5	MANE Select	c.2583-12119C>T		intron	N/A	NP_057422.3
	IPO11	NM_001134779.2		c.2703-12119C>T		intron	N/A	NP_001128251.1	Q9UI26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC70	ENST00000334994.6	TSL:1 MANE Select	c.20C>T	p.Ser7Phe	missense	Exon 2 of 2	ENSP00000399441.1	Q7Z2Q7
	IPO11	ENST00000325324.11	TSL:1 MANE Select	c.2583-12119C>T		intron	N/A	ENSP00000316651.6	Q9UI26-1
	IPO11	ENST00000424533.5	TSL:2	n.*48C>T		non_coding_transcript_exon	Exon 28 of 29	ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.52
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.097
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		0.044	B
Vest4		0.29
MutPred		0.47		Loss of disorder (P = 0.0069)
MVP		0.18
ClinPred		0.15	T
GERP RS		4.3
Varity_R		0.054
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr5-61875285; COSMIC: COSV100320335; COSMIC: COSV100320335;