5-62579814-G-C

Position:

• chr5-62579814-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000334994.6(LRRC70):​c.376G>C​(p.Gly126Arg) variant causes a missense change. 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: LRRC70 ENST00000334994.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

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]

LRRC70 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34550065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC70	NM_181506.5	c.376G>C	p.Gly126Arg	missense_variant	2/2	ENST00000334994.6	NP_852607.3
IPO11	NM_016338.5	c.2583-11763G>C		intron_variant		ENST00000325324.11	NP_057422.3
IPO11	NM_001134779.2	c.2703-11763G>C		intron_variant			NP_001128251.1
IPO11-LRRC70	NR_073584.1	n.201+879G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC70	ENST00000334994.6	c.376G>C	p.Gly126Arg	missense_variant	2/2	1	NM_181506.5	ENSP00000399441.1
IPO11	ENST00000325324.11	c.2583-11763G>C		intron_variant		1	NM_016338.5	ENSP00000316651.6
IPO11	ENST00000424533.5	n.*73+331G>C		intron_variant		2		ENSP00000395685.1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.376G>C (p.G126R) alteration is located in exon 2 (coding exon 1) of the LRRC70 gene. This alteration results from a G to C substitution at nucleotide position 376, causing the glycine (G) at amino acid position 126 to be replaced by an arginine (R). 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	0.30
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		0.77	P
Vest4		0.36
MutPred		0.52		Gain of MoRF binding (P = 0.0077);
MVP		0.47
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.56
gMVP		0.83

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: chr5-61875641;