Variant 1-70148603-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000370952.4(LRRC40):c.1587G>C(p.Gln529His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LRRC40
ENST00000370952.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

LRRC40 (HGNC:26004): (leucine rich repeat containing 40) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC40 links:

LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC40	NM_017768.5 linkuse as main transcript	c.1587G>C	p.Gln529His	missense_variant	14/15	ENST00000370952.4	NP_060238.3
LRRC40	XM_011541763.2 linkuse as main transcript	c.933G>C	p.Gln311His	missense_variant	12/13		XP_011540065.1
LRRC40	XM_047424520.1 linkuse as main transcript	c.933G>C	p.Gln311His	missense_variant	12/13		XP_047280476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC40	ENST00000370952.4 linkuse as main transcript	c.1587G>C	p.Gln529His	missense_variant	14/15	1	NM_017768.5	ENSP00000359990	P1
LRRC7	ENST00000441830.1 linkuse as main transcript	n.192+598C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460964

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.1587G>C (p.Q529H) alteration is located in exon 14 (coding exon 14) of the LRRC40 gene. This alteration results from a G to C substitution at nucleotide position 1587, causing the glutamine (Q) at amino acid position 529 to be replaced by a histidine (H). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

REVEL

Benign

0.24

Sift

Benign

0.10

Sift4G

Benign

0.24

Polyphen

0.92

Vest4

0.57

MutPred

0.39

Loss of stability (P = 0.1052);

MVP

0.75

MPC

0.098

ClinPred

0.97

GERP RS

4.6

Varity_R

0.31

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over