Genetic Variant NM_001012301.4:c.312-121T>A (chr5-150298733-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012301.4(ARSI):c.312-121T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARSI
NM_001012301.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.312-121T>A		intron_variant	Intron 1 of 1	ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ARSI	ENST00000328668.8 link	c.312-121T>A	intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2 link	c.-118-121T>A	intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1 link	c.-118-121T>A	intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

699776

Hom.:

AF XY:

0.00

AC XY:

AN XY:

355242

African (AFR)

AF:

0.00

AC:

AN:

16854

American (AMR)

AF:

0.00

AC:

AN:

19370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15198

East Asian (EAS)

AF:

0.00

AC:

AN:

32304

South Asian (SAS)

AF:

0.00

AC:

AN:

50802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2430

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

484974

Other (OTH)

AF:

0.00

AC:

AN:

33960

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.95

(source)

DANN

Benign

0.53

PhyloP100

-0.81

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over