5-122077513-C-G

Variant names:

• chr5-122077513-C-G
• NM_002317.7:c.473G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002317.7(LOX):​c.473G>C​(p.Arg158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LOX NM_002317.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

LOX (HGNC:6664): (lysyl oxidase) This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections. [provided by RefSeq, Jul 2016]

SRFBP1 (HGNC:26333): (serum response factor binding protein 1) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA. Predicted to be located in perinuclear region of cytoplasm. Predicted to be part of 90S preribosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06293774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOX	NM_002317.7	c.473G>C	p.Arg158Pro	missense_variant	Exon 1 of 7	ENST00000231004.5	NP_002308.2
SRFBP1	XM_017009111.3	c.*2188C>G		3_prime_UTR_variant	Exon 8 of 8		XP_016864600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOX	ENST00000231004.5	c.473G>C	p.Arg158Pro	missense_variant	Exon 1 of 7	1	NM_002317.7	ENSP00000231004.4
LOX	ENST00000639739.2	n.473G>C		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000492324.2
LOX	ENST00000508067.1	n.-41G>C		upstream_gene_variant		4		ENSP00000427538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.8
DANN	Benign	0.81
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.18	N;.
REVEL	Benign	0.034
Sift	Benign	0.34	T;.
Sift4G	Benign	0.25	T;.
Polyphen		0.17	B;B
Vest4		0.24
MutPred		0.23		Gain of glycosylation at R158 (P = 0.045);Gain of glycosylation at R158 (P = 0.045);
MVP		0.33
MPC		0.77
ClinPred		0.093	T
GERP RS		2.4
Varity_R		0.12
gMVP		0.62

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: chr5-121413208;