3-3845100-C-T

Variant names:

• chr3-3845100-C-T
• rs113168029
• NM_020873.7:c.459C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_020873.7(LRRN1):​c.459C>T​(p.Asn153Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,614,056 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (66 hom.)
• Consequence: LRRN1 NM_020873.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.98
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-3845100-C-T is Benign according to our data. Variant chr3-3845100-C-T is described in ClinVar as [Benign]. Clinvar id is 778063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.98 with no splicing effect.
• BS2: High AC in GnomAd4 at 871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 2 of 2	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 3 of 3		NP_001311117.1
LRRN1	NM_001324189.2	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 3 of 3		NP_001311118.1
LRRN1	XM_047448644.1	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 2 of 2		XP_047304600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4	c.459C>T	p.Asn153Asn	synonymous_variant	Exon 2 of 2	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.1192-17591G>A		intron_variant	Intron 9 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152106 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00976

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00501 AC: 1257 AN: 251008 AF XY: 0.00503

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00866

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00821 AC: 12002 AN: 1461832 Hom.: 66 Cov.: 75 AF XY: 0.00802 AC XY: 5831 AN XY: 727220

African (AFR) AF: 0.00116 AC: 39 AN: 33478

American (AMR) AF: 0.00423 AC: 189 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 57 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00173 AC: 149 AN: 86258

European-Finnish (FIN) AF: 0.00137 AC: 73 AN: 53418

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.00997 AC: 11088 AN: 1111968

Other (OTH) AF: 0.00639 AC: 386 AN: 60392

GnomAD4 genome AF: 0.00572 AC: 871 AN: 152224 Hom.: 6 Cov.: 32 AF XY: 0.00499 AC XY: 371 AN XY: 74420

African (AFR) AF: 0.00185 AC: 77 AN: 41534

American (AMR) AF: 0.00569 AC: 87 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00973 AC: 662 AN: 68018

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00846 Hom.: 13

Bravo AF: 0.00634

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.00802

EpiControl AF: 0.00800

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.1
DANN	Benign	0.81
PhyloP100		2.0
Mutation Taster		=98/2	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: rs113168029; hg19: chr3-3886784; COSMIC: COSV100076361; COSMIC: COSV100076361;