NM_021930.6:c.1348dupA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_021930.6(RINT1):c.1348dupA(p.Met450AsnfsTer16) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
RINT1
NM_021930.6 frameshift
NM_021930.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.15
Publications
0 publications found
Genes affected
RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]
RINT1 Gene-Disease associations (from GenCC):
- infantile liver failure syndrome 3Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- infantile liver failure syndrome 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- breast cancerInheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- familial ovarian cancerInheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-105551578-C-CA is Pathogenic according to our data. Variant chr7-105551578-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 410783.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_021930.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| RINT1 | NM_021930.6 | MANE Select | c.1348dupA | p.Met450AsnfsTer16 | frameshift | Exon 10 of 15 | NP_068749.3 | ||
| RINT1 | NM_001346599.2 | c.1114dupA | p.Met372AsnfsTer16 | frameshift | Exon 10 of 15 | NP_001333528.1 | |||
| RINT1 | NM_001346601.2 | c.424dupA | p.Met142AsnfsTer16 | frameshift | Exon 10 of 15 | NP_001333530.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RINT1 | ENST00000257700.7 | TSL:1 MANE Select | c.1348dupA | p.Met450AsnfsTer16 | frameshift | Exon 10 of 15 | ENSP00000257700.2 | Q6NUQ1 | |
| RINT1 | ENST00000967558.1 | c.1477dupA | p.Met493AsnfsTer16 | frameshift | Exon 10 of 15 | ENSP00000637617.1 | |||
| RINT1 | ENST00000899074.1 | c.1348dupA | p.Met450AsnfsTer16 | frameshift | Exon 10 of 16 | ENSP00000569133.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445210Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 718344 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1445210
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
718344
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32852
American (AMR)
AF:
AC:
0
AN:
41772
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25628
East Asian (EAS)
AF:
AC:
0
AN:
39204
South Asian (SAS)
AF:
AC:
1
AN:
83374
European-Finnish (FIN)
AF:
AC:
0
AN:
53144
Middle Eastern (MID)
AF:
AC:
0
AN:
5686
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1103896
Other (OTH)
AF:
AC:
0
AN:
59654
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.225
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational 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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