3-3845037-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020873.7(LRRN1):c.396C>T(p.Thr132Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,613,926 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 4 hom. )

Consequence

LRRN1
NM_020873.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.25

Publications

14 publications found

Variant links:

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]

LRRN1 links:

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

SUMF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-3845037-C-T is Benign according to our data. Variant chr3-3845037-C-T is described in ClinVar as Benign. ClinVar VariationId is 716843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00529 (805/152080) while in subpopulation AFR AF = 0.0188 (779/41450). AF 95% confidence interval is 0.0177. There are 9 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 805 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7 link	c.396C>T	p.Thr132Thr	synonymous_variant	Exon 2 of 2	ENST00000319331.4	NP_065924.3	Q6UXK5A8K6Q2
LRRN1	NM_001324188.2 link	c.396C>T	p.Thr132Thr	synonymous_variant	Exon 3 of 3		NP_001311117.1	Q6UXK5
LRRN1	NM_001324189.2 link	c.396C>T	p.Thr132Thr	synonymous_variant	Exon 3 of 3		NP_001311118.1	Q6UXK5
LRRN1	XM_047448644.1 link	c.396C>T	p.Thr132Thr	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 link	c.396C>T	p.Thr132Thr	synonymous_variant	Exon 2 of 2	1	NM_020873.7	ENSP00000314901.3		Q6UXK5
SUMF1	ENST00000448413.5 link	n.1192-17528G>A		intron_variant	Intron 9 of 12	2		ENSP00000404384.1		F5GXA0

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

806

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

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:

0.00383

GnomAD2 exomes

AF:

0.00148

AC:

372

AN:

251112

AF XY:

0.00106

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000506

AC:

740

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

318

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0188

AC:

628

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111996

Other (OTH)

AF:

0.000695

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00529

AC:

805

AN:

152080

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

366

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0188

AC:

779

AN:

41450

American (AMR)

AF:

0.000850

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67996

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000193

Hom.:

3440

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.81

CADD

Benign

0.50

(source)

DANN

Benign

0.85

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over