rs587776686
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004970.3(IGFALS):c.103delG(p.Glu35LysfsTer87) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,597,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
IGFALS
NM_004970.3 frameshift
NM_004970.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.342
Genes affected
IGFALS (HGNC:5468): (insulin like growth factor binding protein acid labile subunit) The protein encoded by this gene is a serum protein that binds insulin-like growth factors, increasing their half-life and their vascular localization. Production of the encoded protein, which contains twenty leucine-rich repeats, is stimulated by growth hormone. Defects in this gene are a cause of acid-labile subunit deficiency, which maifests itself in a delayed and slow puberty. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 25 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-1792314-TC-T is Pathogenic according to our data. Variant chr16-1792314-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 8127.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-1792314-TC-T is described in Lovd as [Pathogenic]. Variant chr16-1792314-TC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IGFALS | NM_004970.3 | c.103delG | p.Glu35LysfsTer87 | frameshift_variant | Exon 2 of 2 | ENST00000215539.4 | NP_004961.1 | |
| IGFALS | NM_001146006.2 | c.217delG | p.Glu73LysfsTer87 | frameshift_variant | Exon 2 of 2 | NP_001139478.1 | ||
| IGFALS | NR_027389.1 | n.157delG | non_coding_transcript_exon_variant | Exon 2 of 2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IGFALS | ENST00000215539.4 | c.103delG | p.Glu35LysfsTer87 | frameshift_variant | Exon 2 of 2 | 1 | NM_004970.3 | ENSP00000215539.3 | ||
| IGFALS | ENST00000415638.3 | c.217delG | p.Glu73LysfsTer87 | frameshift_variant | Exon 2 of 2 | 2 | ENSP00000416683.3 | |||
| IGFALS | ENST00000568221.1 | c.135delG | p.Lys46SerfsTer16 | frameshift_variant | Exon 2 of 2 | 4 | ENSP00000456923.1 | |||
| SPSB3 | ENST00000569769.1 | c.-13+1322delG | intron_variant | Intron 1 of 4 | 3 | ENSP00000455098.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152122
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00 AC: 0AN: 222216 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
222216
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000346 AC: 5AN: 1444888Hom.: 0 Cov.: 35 AF XY: 0.00000417 AC XY: 3AN XY: 719060 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1444888
Hom.:
Cov.:
35
AF XY:
AC XY:
3
AN XY:
719060
Gnomad4 AFR exome
AF:
AC:
1
AN:
33422
Gnomad4 AMR exome
AF:
AC:
0
AN:
44556
Gnomad4 ASJ exome
AF:
AC:
0
AN:
26048
Gnomad4 EAS exome
AF:
AC:
0
AN:
39630
Gnomad4 SAS exome
AF:
AC:
0
AN:
86094
Gnomad4 FIN exome
AF:
AC:
0
AN:
38984
Gnomad4 NFE exome
AF:
AC:
0
AN:
1110448
Gnomad4 Remaining exome
AF:
AC:
4
AN:
60028
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome 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
GnomAD4 genome 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74296 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152122
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74296
Gnomad4 AFR
AF:
AC:
0.0000241476
AN:
0.0000241476
Gnomad4 AMR
AF:
AC:
0
AN:
0
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
AF:
AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0
AN:
0
Gnomad4 FIN
AF:
AC:
0
AN:
0
Gnomad4 NFE
AF:
AC:
0
AN:
0
Gnomad4 OTH
AF:
AC:
0
AN:
0
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Short stature due to primary acid-labile subunit deficiency Pathogenic:1
Feb 05, 2004
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mutation Taster
=13/187
disease causing (ClinVar)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at