Variant 7-134148287-C-A 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.638C>A(p.Ala213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,602,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

LRGUK
NM_144648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07526338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRGUK	NM_144648.3 linkuse as main transcript	c.638C>A	p.Ala213Glu	missense_variant	5/20	ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRGUK	ENST00000285928.3 linkuse as main transcript	c.638C>A	p.Ala213Glu	missense_variant	5/20	1	NM_144648.3	P2
LRGUK	ENST00000695542.2 linkuse as main transcript	c.638C>A	p.Ala213Glu	missense_variant	5/16			A2
LRGUK	ENST00000645682.1 linkuse as main transcript	c.638C>A	p.Ala213Glu	missense_variant	5/16			A2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000374

AC:

AN:

240384

Hom.:

AF XY:

0.0000308

AC XY:

AN XY:

129686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000512

Gnomad SAS 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:

0.00000828

AC:

AN:

1449920

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000279

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000364

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Mar 18, 2024

The c.638C>A (p.A213E) alteration is located in exon 5 (coding exon 5) of the LRGUK gene. This alteration results from a C to A substitution at nucleotide position 638, causing the alanine (A) at amino acid position 213 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.0022

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

.;N

MutationTaster

Benign

0.95

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.2

.;N

REVEL

Benign

0.074

Sift

Benign

0.33

.;T

Sift4G

Uncertain

0.017

.;D

Polyphen

0.66

.;P

Vest4

0.27

MutPred

0.41

Gain of solvent accessibility (P = 0.1185);Gain of solvent accessibility (P = 0.1185);

MVP

0.37

MPC

0.083

ClinPred

0.076

GERP RS

4.9

Varity_R

0.30

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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