17-3476008-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000049.4(ASPA):​c.-152C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000952 in 714,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

ASPA
NM_000049.4 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.310

Publications

0 publications found
Variant links:
Genes affected
ASPA (HGNC:756): (aspartoacylase) This gene encodes an enzyme that catalyzes the conversion of N-acetyl_L-aspartic acid (NAA) to aspartate and acetate. NAA is abundant in the brain where hydrolysis by aspartoacylase is thought to help maintain white matter. This protein is an NAA scavenger in other tissues. Mutations in this gene cause Canavan disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]
SPATA22 Gene-Disease associations (from GenCC):
  • infertility disorder
    Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASPANM_000049.4 linkc.-152C>T 5_prime_UTR_variant Exon 1 of 6 ENST00000263080.3 NP_000040.1 P45381Q6FH48

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASPAENST00000263080.3 linkc.-152C>T 5_prime_UTR_variant Exon 1 of 6 1 NM_000049.4 ENSP00000263080.2 P45381

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00270
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000943
AC:
53
AN:
561858
Hom.:
0
Cov.:
8
AF XY:
0.0000809
AC XY:
24
AN XY:
296704
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
14624
American (AMR)
AF:
0.00
AC:
0
AN:
23550
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16162
East Asian (EAS)
AF:
0.00151
AC:
48
AN:
31836
South Asian (SAS)
AF:
0.0000391
AC:
2
AN:
51108
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
30728
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2290
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
361530
Other (OTH)
AF:
0.0000999
AC:
3
AN:
30030
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.0000985
AC:
15
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41552
American (AMR)
AF:
0.0000654
AC:
1
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00270
AC:
14
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.000125

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spongy degeneration of central nervous system Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
15
DANN
Benign
0.86
PhyloP100
0.31
PromoterAI
-0.15
Neutral
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs886052821; hg19: chr17-3379302; API