Variant 7-134174605-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144648.3(LRGUK):c.989G>A(p.Arg330Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,455,640 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: 0.000032 ( 0 hom. )

Consequence

LRGUK
NM_144648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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:

Genome browser will be placed here

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	UniProt
LRGUK	NM_144648.3 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	8/20	ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRGUK	ENST00000285928.3 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	8/20	1	NM_144648.3	P2
LRGUK	ENST00000695542.2 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	8/16			A2
LRGUK	ENST00000645682.1 linkuse as main transcript	c.989G>A	p.Arg330Gln	missense_variant	8/16			A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250322

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1455640

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

724622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000398

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Jan 05, 2022

The c.989G>A (p.R330Q) alteration is located in exon 8 (coding exon 8) of the LRGUK gene. This alteration results from a G to A substitution at nucleotide position 989, causing the arginine (R) at amino acid position 330 to be replaced by a glutamine (Q). 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

0.42

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.0

.;M

MutationTaster

Benign

0.91

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.19

Sift

Benign

0.072

.;T

Sift4G

Uncertain

0.034

.;D

Polyphen

1.0

.;D

Vest4

0.42

MutPred

0.52

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.76

MPC

0.33

ClinPred

0.96

GERP RS

5.4

Varity_R

0.31

gMVP

0.38

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