rs869320724
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001374504.1(TMPRSS6):c.1877_1878dupGC(p.Lys627AlafsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000008 in 124,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000080 ( 0 hom., cov: 32)
Consequence
TMPRSS6
NM_001374504.1 frameshift
NM_001374504.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.108
Publications
3 publications found
Genes affected
TMPRSS6 (HGNC:16517): (transmembrane serine protease 6) The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
TMPRSS6 Gene-Disease associations (from GenCC):
- IRIDA syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, PanelApp Australia, Orphanet
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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-37069307-T-TGC is Pathogenic according to our data. Variant chr22-37069307-T-TGC is described in ClinVar as Pathogenic. ClinVar VariationId is 1399.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001374504.1. 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 |
|---|---|---|---|---|---|---|---|---|---|
| TMPRSS6 | MANE Select | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 18 | NP_001361433.1 | Q8IU80-1 | ||
| TMPRSS6 | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 19 | NP_001275929.1 | Q8IU80-5 | |||
| TMPRSS6 | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 18 | NP_001275930.1 | Q8IU80-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TMPRSS6 | MANE Select | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 18 | ENSP00000501573.1 | Q8IU80-1 | ||
| TMPRSS6 | TSL:1 | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 19 | ENSP00000384964.1 | Q8IU80-5 | ||
| TMPRSS6 | TSL:1 | c.1877_1878dupGC | p.Lys627AlafsTer17 | frameshift | Exon 16 of 18 | ENSP00000334962.6 | Q8IU80-1 |
Frequencies
GnomAD3 genomes 0.00000800 AC: 1AN: 124966Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
124966
Hom.:
Cov.:
32
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:
GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome 0.00000800 AC: 1AN: 124966Hom.: 0 Cov.: 32 AF XY: 0.0000171 AC XY: 1AN XY: 58400 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
124966
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
58400
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32900
American (AMR)
AF:
AC:
0
AN:
10378
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3276
East Asian (EAS)
AF:
AC:
0
AN:
3528
South Asian (SAS)
AF:
AC:
0
AN:
3624
European-Finnish (FIN)
AF:
AC:
0
AN:
5720
Middle Eastern (MID)
AF:
AC:
0
AN:
218
European-Non Finnish (NFE)
AF:
AC:
1
AN:
62716
Other (OTH)
AF:
AC:
0
AN:
1744
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
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
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Iron-refractory iron deficiency anemia (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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