chr22-37069345-C-CTGGGGTGGGGTGGGGTGGGG
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PVS1_StrongBP6_ModerateBS1
The NM_001374504.1(TMPRSS6):c.1842-2_1842-1insCCCCACCCCACCCCACCCCA variant causes a splice acceptor change. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00026 ( 1 hom., cov: 0)
Exomes 𝑓: 0.000043 ( 0 hom. )
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 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-CTGGGGTGGGGTGGGGTGGGG is Benign according to our data. Variant chr22-37069345-C-CTGGGGTGGGGTGGGGTGGGG is described in ClinVar as [Likely_benign]. Clinvar id is 3054932.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000264 (24/91028) while in subpopulation AFR AF= 0.000862 (23/26688). AF 95% confidence interval is 0.000588. There are 1 homozygotes in gnomad4. There are 11 alleles in male gnomad4 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_1842-1insCCCCACCCCACCCCACCCCA | splice_acceptor_variant | ENST00000676104.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS6 | ENST00000676104.1 | c.1842-2_1842-1insCCCCACCCCACCCCACCCCA | splice_acceptor_variant | NM_001374504.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000242 AC: 22AN: 90956Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.0000427 AC: 14AN: 327526Hom.: 0 Cov.: 0 AF XY: 0.0000294 AC XY: 5AN XY: 170130
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GnomAD4 genome ? AF: 0.000264 AC: 24AN: 91028Hom.: 1 Cov.: 0 AF XY: 0.000255 AC XY: 11AN XY: 43058
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TMPRSS6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at