chr7-134183825-A-G

Position:

• chr7-134183825-A-G

Variant summary

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

The NM_144648.3(LRGUK):​c.1306A>G​(p.Arg436Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRGUK NM_144648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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]

ACMG classification

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	c.1306A>G	p.Arg436Gly	missense_variant	11/20	ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRGUK	ENST00000285928.3	c.1306A>G	p.Arg436Gly	missense_variant	11/20	1	NM_144648.3	P2
LRGUK	ENST00000695542.2	c.1306A>G	p.Arg436Gly	missense_variant	11/16			A2
LRGUK	ENST00000645682.1	c.1306A>G	p.Arg436Gly	missense_variant	11/16			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1306A>G (p.R436G) alteration is located in exon 11 (coding exon 11) of the LRGUK gene. This alteration results from a A to G substitution at nucleotide position 1306, causing the arginine (R) at amino acid position 436 to be replaced by a glycine (G). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	.;M
MutationTaster	Benign	0.55	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.6	.;D
REVEL	Benign	0.16
Sift	Uncertain	0.011	.;D
Sift4G	Uncertain	0.0050	.;D
Polyphen		0.99	.;D
Vest4		0.69
MutPred		0.48		Loss of MoRF binding (P = 0.0126);Loss of MoRF binding (P = 0.0126);
MVP		0.34
MPC		0.34
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.62
gMVP		0.51

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.

Other links and lift over

hg19: chr7-133868577;