Genetic Variant LRGUK:p.Glu89Gly (chr7-134127633-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144648.3(LRGUK):c.266A>G(p.Glu89Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

LRGUK
NM_144648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.284

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10094234).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144648.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRGUK	NM_144648.3	MANE Select	c.266A>G	p.Glu89Gly	missense	Exon 1 of 20	NP_653249.1	Q96M69
LRGUK	NM_001365700.3		c.266A>G	p.Glu89Gly	missense	Exon 1 of 16	NP_001352629.1	A0A8Q3SI13
LRGUK	NM_001365701.3		c.266A>G	p.Glu89Gly	missense	Exon 1 of 16	NP_001352630.1	A0A2R8YEJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRGUK	ENST00000285928.3	TSL:1 MANE Select	c.266A>G	p.Glu89Gly	missense	Exon 1 of 20	ENSP00000285928.2	Q96M69
LRGUK	ENST00000695542.2		c.266A>G	p.Glu89Gly	missense	Exon 1 of 16	ENSP00000511999.1	A0A8Q3SI13
LRGUK	ENST00000645682.1		c.266A>G	p.Glu89Gly	missense	Exon 1 of 16	ENSP00000495637.1	A0A2R8YEJ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251066

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000246

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111896

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.52

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

PhyloP100

0.28

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.054

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.014

Polyphen

0.44

Vest4

0.32

MutPred

0.27

Loss of stability (P = 0.1629)

MVP

0.41

MPC

0.13

ClinPred

0.24

GERP RS

2.6

PromoterAI

0.00080

Neutral

(source)

Varity_R

0.071

gMVP

0.29

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over