6-31859509-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000434.4(NEU1):c.*210T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 657,548 control chromosomes in the GnomAD database, including 813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 279 hom., cov: 32)

Exomes 𝑓: 0.039 ( 534 hom. )

Consequence

NEU1
NM_000434.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.112

Publications

22 publications found

Variant links:

Genes affected

NEU1 (HGNC:7758): (neuraminidase 1) The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]

NEU1 Gene-Disease associations (from GenCC):

sialidosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
sialidosis type 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital sialidosis type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
juvenile sialidosis type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
sialidosis type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEU1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-31859509-A-T is Benign according to our data. Variant chr6-31859509-A-T is described in ClinVar as Benign. ClinVar VariationId is 356229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEU1	NM_000434.4 link	c.*210T>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000375631.5	NP_000425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEU1	ENST00000375631.5 link	c.*210T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_000434.4	ENSP00000364782.4

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7935

AN:

152170

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0999

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0344

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0540

GnomAD4 exome

AF:

0.0385

AC:

19456

AN:

505260

Hom.:

534

Cov.:

AF XY:

0.0379

AC XY:

10239

AN XY:

270388

show subpopulations

African (AFR)

AF:

0.101

AC:

1468

AN:

14502

American (AMR)

AF:

0.0305

AC:

911

AN:

29880

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

1363

AN:

16518

East Asian (EAS)

AF:

0.0588

AC:

1863

AN:

31690

South Asian (SAS)

AF:

0.0277

AC:

1499

AN:

54138

European-Finnish (FIN)

AF:

0.0322

AC:

1007

AN:

31284

Middle Eastern (MID)

AF:

0.0580

AC:

130

AN:

2242

European-Non Finnish (NFE)

AF:

0.0339

AC:

10068

AN:

296590

Other (OTH)

AF:

0.0404

AC:

1147

AN:

28416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1142

2283

3425

4566

5708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0522

AC:

7944

AN:

152288

Hom.:

279

Cov.:

AF XY:

0.0523

AC XY:

3892

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.100

AC:

4154

AN:

41552

American (AMR)

AF:

0.0303

AC:

463

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

257

AN:

3472

East Asian (EAS)

AF:

0.0376

AC:

195

AN:

5182

South Asian (SAS)

AF:

0.0271

AC:

131

AN:

4830

European-Finnish (FIN)

AF:

0.0344

AC:

365

AN:

10610

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0329

AC:

2239

AN:

68020

Other (OTH)

AF:

0.0534

AC:

113

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

390

780

1171

1561

1951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0412

Hom.:

Bravo

AF:

0.0555

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sialidosis type 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not provided

Benign:1

Dec 31, 2018

GeneDx

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

-0.82

CADD

Benign

3.5

(source)

DANN

Benign

0.62

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(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