Genetic Variant ARSI:c.312-150T>C (chr5-150298762-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012301.4(ARSI):c.312-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 668,200 control chromosomes in the GnomAD database, including 274,686 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 0.89 ( 59906 hom., cov: 32)

Exomes 𝑓: 0.91 ( 214780 hom. )

Consequence

ARSI
NM_001012301.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.128

Publications

3 publications found

Variant links:

Genes affected

ARSI (HGNC:32521): (arylsulfatase family member I) This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

ARSI Gene-Disease associations (from GenCC):

autosomal recessive spastic paraplegia type 66
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ARSI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.312-150T>C		intron_variant	Intron 1 of 1	ENST00000328668.8	NP_001012301.1	Q5FYB1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSI	ENST00000328668.8 link	c.312-150T>C	intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7	Q5FYB1-1
ARSI	ENST00000515301.2 link	c.-118-150T>C	intron_variant	Intron 1 of 1	4		ENSP00000426879.2	Q5FYB1-2
ARSI	ENST00000509146.1 link	c.-118-150T>C	intron_variant	Intron 1 of 1	4		ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134657

AN:

152096

Hom.:

59856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.868

Gnomad SAS

AF:

0.881

Gnomad FIN

AF:

0.957

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.929

Gnomad OTH

AF:

0.874

GnomAD4 exome

AF:

0.911

AC:

470130

AN:

515984

Hom.:

214780

AF XY:

0.910

AC XY:

243639

AN XY:

267736

show subpopulations

African (AFR)

AF:

0.832

AC:

11183

AN:

13448

American (AMR)

AF:

0.743

AC:

13796

AN:

18556

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

12489

AN:

14040

East Asian (EAS)

AF:

0.871

AC:

27238

AN:

31290

South Asian (SAS)

AF:

0.876

AC:

40986

AN:

46770

European-Finnish (FIN)

AF:

0.954

AC:

37500

AN:

39288

Middle Eastern (MID)

AF:

0.850

AC:

1765

AN:

2076

European-Non Finnish (NFE)

AF:

0.930

AC:

299909

AN:

322512

Other (OTH)

AF:

0.902

AC:

25264

AN:

28004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2258

4516

6773

9031

11289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2260

4520

6780

9040

11300

<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:

0.885

AC:

134762

AN:

152216

Hom.:

59906

Cov.:

AF XY:

0.884

AC XY:

65818

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.832

AC:

34520

AN:

41490

American (AMR)

AF:

0.793

AC:

12128

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3081

AN:

3472

East Asian (EAS)

AF:

0.868

AC:

4493

AN:

5178

South Asian (SAS)

AF:

0.882

AC:

4251

AN:

4822

European-Finnish (FIN)

AF:

0.957

AC:

10159

AN:

10616

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.929

AC:

63162

AN:

68016

Other (OTH)

AF:

0.875

AC:

1852

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

790

1579

2369

3158

3948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.898

Hom.:

7661

Bravo

AF:

0.868

Asia WGS

AF:

0.877

AC:

3049

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.2

(source)

DANN

Benign

0.66

PhyloP100

0.13

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

Computational scores

Splicing

Publications

Other links and lift over