10-98253581-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032211.7(LOXL4):​c.1807G>A​(p.Asp603Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

LOXL4
NM_032211.7 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
LOXL4 (HGNC:17171): (lysyl oxidase like 4) This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28301048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LOXL4NM_032211.7 linkc.1807G>A p.Asp603Asn missense_variant Exon 11 of 15 ENST00000260702.4 NP_115587.6 Q96JB6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LOXL4ENST00000260702.4 linkc.1807G>A p.Asp603Asn missense_variant Exon 11 of 15 1 NM_032211.7 ENSP00000260702.3 Q96JB6
ENSG00000230928ENST00000433374.1 linkn.180+1379C>T intron_variant Intron 1 of 1 1

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251464
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461888
Hom.:
0
Cov.:
33
AF XY:
0.0000220
AC XY:
16
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1807G>A (p.D603N) alteration is located in exon 11 (coding exon 10) of the LOXL4 gene. This alteration results from a G to A substitution at nucleotide position 1807, causing the aspartic acid (D) at amino acid position 603 to be replaced by an asparagine (N). 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
0.082
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.25
N
REVEL
Benign
0.094
Sift
Uncertain
0.023
D
Sift4G
Benign
0.17
T
Polyphen
0.16
B
Vest4
0.33
MVP
0.35
MPC
0.12
ClinPred
0.13
T
GERP RS
4.0
Varity_R
0.062
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372106198; hg19: chr10-100013338; COSMIC: COSV99584301; API