dbSNP rs752839330: LOX:p.Ala79Ser (chr5-122077751-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002317.7(LOX):c.235G>T(p.Ala79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A79T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LOX
NM_002317.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.319

Publications

0 publications found

Variant links:

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]

LOX links:

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]

SRFBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06849322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOX	NM_002317.7 link	c.235G>T	p.Ala79Ser	missense_variant	Exon 1 of 7	ENST00000231004.5	NP_002308.2	P28300D0PNI2
SRFBP1	XM_017009111.3 link	c.*2426C>A		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 link	c.235G>T	p.Ala79Ser	missense_variant	Exon 1 of 7	1	NM_002317.7	ENSP00000231004.4		P28300
LOX	ENST00000639739.2 link	n.235G>T		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000492324.2		A0A7P0SNB0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1410310

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32196

American (AMR)

AF:

0.00

AC:

AN:

37862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25272

East Asian (EAS)

AF:

0.00

AC:

AN:

37310

South Asian (SAS)

AF:

0.00

AC:

AN:

81556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090834

Other (OTH)

AF:

0.00

AC:

AN:

58630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.62

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.41

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N

PhyloP100

0.32

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.016

Sift

Benign

0.052

T;.

Sift4G

Benign

0.81

T;.

Polyphen

0.0

B;B

Vest4

0.092

MutPred

0.14

Gain of glycosylation at A79 (P = 0.0016);Gain of glycosylation at A79 (P = 0.0016);

MVP

0.22

MPC

0.49

ClinPred

0.047

GERP RS

-0.81

Varity_R

0.060

gMVP

0.34

Mutation Taster

=92/8

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over