rs10510278

Variant names:

• chr3-3820397-T-A
• rs10510278
• NM_020873.7:c.-279+20478T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-3820397-T-A
• chr3-3820397-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020873.7(LRRN1):​c.-279+20478T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,240 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.059 (300 hom., cov: 33)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 3 publications found

Genes affected

LRRN1 (HGNC:20980): (leucine rich repeat neuronal 1) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN1	NM_020873.7	MANE Select	c.-279+20478T>A		intron	N/A	NP_065924.3
	LRRN1	NM_001324188.2		c.-279+19151T>A		intron	N/A	NP_001311117.1
	LRRN1	NM_001324189.2		c.-279+19151T>A		intron	N/A	NP_001311118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN1	ENST00000319331.4	TSL:1 MANE Select	c.-279+20478T>A		intron	N/A	ENSP00000314901.3
	SUMF1	ENST00000448413.5	TSL:2	n.*342+2337A>T		intron	N/A	ENSP00000404384.1
	LRRN1	ENST00000496115.1	TSL:3	n.376+19151T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9050 AN: 152122 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0508

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0594 AC: 9050 AN: 152240 Hom.: 300 Cov.: 33 AF XY: 0.0605 AC XY: 4505 AN XY: 74446

African (AFR) AF: 0.0389 AC: 1616 AN: 41554

American (AMR) AF: 0.0725 AC: 1109 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3470

East Asian (EAS) AF: 0.0526 AC: 273 AN: 5188

South Asian (SAS) AF: 0.0863 AC: 416 AN: 4822

European-Finnish (FIN) AF: 0.0868 AC: 921 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4341 AN: 67984

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0616 Hom.: 42

Bravo AF: 0.0581

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.80
PhyloP100		-0.85
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: rs10510278; hg19: chr3-3862081;