NM_005576.4:c.478G>C

Variant names:

• chr15-73927261-G-C
• rs138183635
• NM_005576.4:c.478G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005576.4(LOXL1):​c.478G>C​(p.Ala160Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,601,692 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (14 hom.)
• Consequence: LOXL1 NM_005576.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 3 publications found

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. 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. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01631403).
• BP6: Variant 15-73927261-G-C is Benign according to our data. Variant chr15-73927261-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2645532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	NM_005576.4	MANE Select	c.478G>C	p.Ala160Pro	missense	Exon 1 of 7	NP_005567.2	Q08397
	LOXL1-AS1	NR_040066.1		n.133+393C>G		intron	N/A
	LOXL1-AS1	NR_040067.1		n.133+393C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.478G>C	p.Ala160Pro	missense	Exon 1 of 7	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.478G>C	p.Ala160Pro	missense	Exon 1 of 6	ENSP00000526690.1
	LOXL1	ENST00000566011.5	TSL:5	n.478G>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000457827.1	H3BUV8

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152156 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00122 AC: 278 AN: 227896 AF XY: 0.00122

Gnomad AFR exome AF: 0.000575

Gnomad AMR exome AF: 0.000331

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000592

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.00248 AC: 3593 AN: 1449428 Hom.: 14 Cov.: 36 AF XY: 0.00238 AC XY: 1717 AN XY: 721378

African (AFR) AF: 0.000552 AC: 18 AN: 32610

American (AMR) AF: 0.000385 AC: 17 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39194

South Asian (SAS) AF: 0.000539 AC: 46 AN: 85392

European-Finnish (FIN) AF: 0.00101 AC: 47 AN: 46600

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00293 AC: 3247 AN: 1109638

Other (OTH) AF: 0.00359 AC: 216 AN: 60096

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152264 Hom.: 1 Cov.: 33 AF XY: 0.00126 AC XY: 94 AN XY: 74450

African (AFR) AF: 0.000577 AC: 24 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 67994

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00192 Hom.: 0

Bravo AF: 0.00141

ESP6500AA AF: 0.000917 AC: 4

ESP6500EA AF: 0.00305 AC: 26

ExAC AF: 0.00122 AC: 147

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.055	T
Polyphen		1.0	D
Vest4		0.50
MVP		0.60
ClinPred		0.014	T
GERP RS		4.1
Varity_R		0.38
gMVP		0.56
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs138183635; hg19: chr15-74219602;