rs35955622
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001352514.2(HLCS):c.*3225_*3226delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 139,394 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HLCS
NM_001352514.2 3_prime_UTR
NM_001352514.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.208
Publications
0 publications found
Genes affected
HLCS (HGNC:4976): (holocarboxylase synthetase) This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]
HLCS Gene-Disease associations (from GenCC):
- holocarboxylase synthetase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001352514.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HLCS | NM_001352514.2 | MANE Select | c.*3225_*3226delTT | 3_prime_UTR | Exon 11 of 11 | NP_001339443.1 | P50747-2 | ||
| HLCS | NM_000411.8 | c.*3225_*3226delTT | 3_prime_UTR | Exon 12 of 12 | NP_000402.3 | ||||
| HLCS | NM_001242784.3 | c.*3225_*3226delTT | 3_prime_UTR | Exon 12 of 12 | NP_001229713.1 | P50747-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HLCS | ENST00000674895.3 | MANE Select | c.*3225_*3226delTT | 3_prime_UTR | Exon 11 of 11 | ENSP00000502087.2 | P50747-2 | ||
| HLCS | ENST00000336648.8 | TSL:1 | c.*3225_*3226delTT | 3_prime_UTR | Exon 12 of 12 | ENSP00000338387.3 | P50747-1 | ||
| HLCS | ENST00000612277.4 | TSL:5 | c.*3225_*3226delTT | 3_prime_UTR | Exon 12 of 12 | ENSP00000479939.1 | P50747-1 |
Frequencies
GnomAD3 genomes 0.0000143 AC: 2AN: 139394Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
139394
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 68Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
68
Hom.:
AF XY:
AC XY:
0
AN XY:
34
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
AC:
0
AN:
68
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AC:
0
AN:
0
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome 0.0000143 AC: 2AN: 139394Hom.: 0 Cov.: 30 AF XY: 0.0000149 AC XY: 1AN XY: 67300 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
139394
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
67300
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
37992
American (AMR)
AF:
AC:
0
AN:
13926
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3316
East Asian (EAS)
AF:
AC:
0
AN:
4926
South Asian (SAS)
AF:
AC:
0
AN:
4288
European-Finnish (FIN)
AF:
AC:
1
AN:
7950
Middle Eastern (MID)
AF:
AC:
0
AN:
296
European-Non Finnish (NFE)
AF:
AC:
1
AN:
63930
Other (OTH)
AF:
AC:
0
AN:
1896
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.250
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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