Variant 7-134127510-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144648.3(LRGUK):c.143A>G(p.Gln48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

LRGUK
NM_144648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

LRGUK (HGNC:21964): (leucine rich repeats and guanylate kinase domain containing) Predicted to enable guanylate kinase activity. Predicted to be involved in axoneme assembly and spermatogenesis. Predicted to be located in acrosomal vesicle and manchette. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRGUK links:

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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=0.076545596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRGUK	NM_144648.3 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	1/20	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRGUK	ENST00000285928.3 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	1/20	1	NM_144648.3	ENSP00000285928	P2
LRGUK	ENST00000695542.2 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	1/16			ENSP00000511999	A2
LRGUK	ENST00000645682.1 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	1/16			ENSP00000495637	A2
LRGUK	ENST00000473068.1 linkuse as main transcript	n.153A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251482

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000603

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 16, 2023

The c.143A>G (p.Q48R) alteration is located in exon 1 (coding exon 1) of the LRGUK gene. This alteration results from a A to G substitution at nucleotide position 143, causing the glutamine (Q) at amino acid position 48 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

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0019

.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

.;N

REVEL

Benign

0.047

Sift

Benign

0.13

.;T

Sift4G

Benign

0.68

.;T

Polyphen

0.079

.;B

Vest4

0.24

MVP

0.37

MPC

0.074

ClinPred

0.056

GERP RS

1.2

Varity_R

0.047

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over