14-21211228-AGTCATCCTCGCCATTGGCGCTGTCTCT-A
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4PP5_Moderate
The NM_004500.4(HNRNPC):c.850_876delAGAGACAGCGCCAATGGCGAGGATGAC(p.Arg284_Asp292del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000657 in 152,104 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Consequence
HNRNPC
NM_004500.4 conservative_inframe_deletion
NM_004500.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.29
Publications
0 publications found
Genes affected
HNRNPC (HGNC:5035): (heterogeneous nuclear ribonucleoprotein C) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Multiple transcript variants encoding at least two different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_004500.4.
PP5
Variant 14-21211228-AGTCATCCTCGCCATTGGCGCTGTCTCT-A is Pathogenic according to our data. Variant chr14-21211228-AGTCATCCTCGCCATTGGCGCTGTCTCT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 973074.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004500.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| HNRNPC | MANE Select | c.850_876delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg284_Asp292del | conservative_inframe_deletion | Exon 9 of 9 | NP_004491.2 | P07910-2 | ||
| HNRNPC | c.889_915delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg297_Asp305del | conservative_inframe_deletion | Exon 8 of 8 | NP_001070910.1 | P07910-1 | |||
| HNRNPC | c.889_915delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg297_Asp305del | conservative_inframe_deletion | Exon 9 of 9 | NP_112604.2 | P07910-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HNRNPC | TSL:1 MANE Select | c.850_876delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg284_Asp292del | conservative_inframe_deletion | Exon 9 of 9 | ENSP00000450544.1 | P07910-2 | ||
| HNRNPC | TSL:1 | c.889_915delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg297_Asp305del | conservative_inframe_deletion | Exon 9 of 9 | ENSP00000451291.1 | P07910-1 | ||
| HNRNPC | TSL:1 | c.889_915delAGAGACAGCGCCAATGGCGAGGATGAC | p.Arg297_Asp305del | conservative_inframe_deletion | Exon 8 of 8 | ENSP00000452276.1 | P07910-1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152104
Hom.:
Cov.:
31
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:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74308 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152104
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74308
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68012
Other (OTH)
AF:
AC:
0
AN:
2090
⚠️ 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: 0.375
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.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
-
-
Intellectual developmental disorder, autosomal dominant 74 (2)
-
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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