rs79201792

Variant names:

• chr2-74532596-T-C
• rs79201792
• NM_032603.5:c.*1010A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74532596-T-C
• chr2-74532596-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032603.5(LOXL3):​c.*1010A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 1,604,318 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (239 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (246 hom.)
• Consequence: LOXL3 NM_032603.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.44
• Publications: 1 publications found

Genes affected

LOXL3 (HGNC:13869): (lysyl oxidase like 3) This gene encodes a lysyl oxidase, which likely functions as an amine oxidase and plays a role in the formation of crosslinks in collagens and elastin. Deletion of the related gene in mouse causes neonatal mortality with cleft palate, spine deformity, and defects in collagen organization. A mutation in this gene was found in a family with Stickler syndrome. [provided by RefSeq, Sep 2016]

HTRA2 (HGNC:14348): (HtrA serine peptidase 2) This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

HTRA2 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria type 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-74532596-T-C is Benign according to our data. Variant chr2-74532596-T-C is described in ClinVar as Benign. ClinVar VariationId is 1296504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032603.5. 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
	LOXL3	NM_032603.5	MANE Select	c.*1010A>G		3_prime_UTR	Exon 14 of 14	NP_115992.1	P58215-1
	HTRA2	NM_013247.5	MANE Select	c.1116-23T>C		intron	N/A	NP_037379.1	O43464-1
	LOXL3	NM_001289164.3		c.*1010A>G		3_prime_UTR	Exon 12 of 12	NP_001276093.1	P58215-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL3	ENST00000264094.8	TSL:1 MANE Select	c.*1010A>G		3_prime_UTR	Exon 14 of 14	ENSP00000264094.3	P58215-1
	HTRA2	ENST00000258080.8	TSL:1 MANE Select	c.1116-23T>C		intron	N/A	ENSP00000258080.3	O43464-1
	HTRA2	ENST00000437202.2	TSL:1	c.1146-224T>C		intron	N/A	ENSP00000399166.2	O43464-3

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4720 AN: 152120 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00837 AC: 2096 AN: 250504 AF XY: 0.00617

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.00485

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00328 AC: 4762 AN: 1452080 Hom.: 246 Cov.: 29 AF XY: 0.00276 AC XY: 1994 AN XY: 723052

African (AFR) AF: 0.117 AC: 3905 AN: 33250

American (AMR) AF: 0.00547 AC: 244 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.000432 AC: 37 AN: 85734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00747 AC: 38 AN: 5084

European-Non Finnish (NFE) AF: 0.000146 AC: 161 AN: 1104280

Other (OTH) AF: 0.00628 AC: 377 AN: 60028

GnomAD4 genome AF: 0.0310 AC: 4726 AN: 152238 Hom.: 239 Cov.: 32 AF XY: 0.0300 AC XY: 2232 AN XY: 74452

African (AFR) AF: 0.109 AC: 4510 AN: 41498

American (AMR) AF: 0.00980 AC: 150 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68032

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.0151 Hom.: 37

Bravo AF: 0.0362

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs79201792; hg19: chr2-74759723;