chr7-134127543-C-T

Position:

• chr7-134127543-C-T

Variant summary

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

The NM_144648.3(LRGUK):​c.176C>T​(p.Ser59Phe) 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: 30)
• Consequence: LRGUK NM_144648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

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	Protein	UniProt
LRGUK	NM_144648.3	c.176C>T	p.Ser59Phe	missense_variant	1/20	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.176C>T	p.Ser59Phe	missense_variant	1/20	1	NM_144648.3	ENSP00000285928.2
LRGUK	ENST00000695542.2	c.176C>T	p.Ser59Phe	missense_variant	1/16			ENSP00000511999.1
LRGUK	ENST00000645682.1	c.176C>T	p.Ser59Phe	missense_variant	1/16			ENSP00000495637.1
LRGUK	ENST00000473068.1	n.186C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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

Nov 22, 2024

The c.176C>T (p.S59F) alteration is located in exon 1 (coding exon 1) of the LRGUK gene. This alteration results from a C to T substitution at nucleotide position 176, causing the serine (S) at amino acid position 59 to be replaced by a phenylalanine (F). 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	0.24
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	.;N
REVEL	Benign	0.15
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		0.70	.;P
Vest4		0.38
MutPred		0.55		Loss of disorder (P = 0.017);Loss of disorder (P = 0.017);
MVP		0.54
MPC		0.29
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.23
gMVP		0.36

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: chr7-133812296;