chr22-37069345-C-CTGGGGTGGGG
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PVS1_StrongBP6_Very_StrongBS1
The NM_001374504.1(TMPRSS6):c.1842-2_1842-1insCCCCACCCCA variant causes a splice acceptor change. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 92 hom., cov: 0)
Exomes 𝑓: 0.0014 ( 11 hom. )
Failed GnomAD Quality Control
Consequence
TMPRSS6
NM_001374504.1 splice_acceptor
NM_001374504.1 splice_acceptor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.94
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.11249481 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.8, offset of 0 (no position change), new splice context is: cccaccccaccccaccccAGcat. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
BP6
?
Variant 22-37069345-C-CTGGGGTGGGG is Benign according to our data. Variant chr22-37069345-C-CTGGGGTGGGG is described in ClinVar as [Likely_benign]. Clinvar id is 786381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00144 (471/327516) while in subpopulation AFR AF= 0.033 (323/9802). AF 95% confidence interval is 0.03. There are 11 homozygotes in gnomad4_exome. There are 204 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS6 | NM_001374504.1 | c.1842-2_1842-1insCCCCACCCCA | splice_acceptor_variant | ENST00000676104.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS6 | ENST00000676104.1 | c.1842-2_1842-1insCCCCACCCCA | splice_acceptor_variant | NM_001374504.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2199AN: 90888Hom.: 91 Cov.: 0 FAILED QC
GnomAD3 genomes
?
AF:
AC:
2199
AN:
90888
Hom.:
Cov.:
0
FAILED QC
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:
GnomAD3 exomes AF: 0.0000680 AC: 5AN: 73502Hom.: 0 AF XY: 0.0000700 AC XY: 3AN XY: 42836
GnomAD3 exomes
AF:
AC:
5
AN:
73502
Hom.:
AF XY:
AC XY:
3
AN XY:
42836
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00144 AC: 471AN: 327516Hom.: 11 Cov.: 0 AF XY: 0.00120 AC XY: 204AN XY: 170118
GnomAD4 exome
AF:
AC:
471
AN:
327516
Hom.:
Cov.:
0
AF XY:
AC XY:
204
AN XY:
170118
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0242 AC: 2201AN: 90960Hom.: 92 Cov.: 0 AF XY: 0.0235 AC XY: 1011AN XY: 43032
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2201
AN:
90960
Hom.:
Cov.:
0
AF XY:
AC XY:
1011
AN XY:
43032
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
TMPRSS6-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 19, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at