chr22-37069345-C-CTGGGG
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_1842-1insCCCCA variant causes a splice acceptor change. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.029 ( 119 hom., cov: 0)
Exomes 𝑓: 0.0018 ( 13 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]
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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-CTGGGG is Benign according to our data. Variant chr22-37069345-C-CTGGGG is described in ClinVar as [Likely_benign]. Clinvar id is 780652.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00179 (585/327500) while in subpopulation AFR AF= 0.0355 (348/9792). AF 95% confidence interval is 0.0325. There are 13 homozygotes in gnomad4_exome. There are 287 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_1842-1insCCCCA | splice_acceptor_variant | ENST00000676104.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS6 | ENST00000676104.1 | c.1842-2_1842-1insCCCCA | splice_acceptor_variant | NM_001374504.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2639AN: 90908Hom.: 116 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.000150 AC: 11AN: 73502Hom.: 0 AF XY: 0.000163 AC XY: 7AN XY: 42836
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GnomAD4 exome AF: 0.00179 AC: 585AN: 327500Hom.: 13 Cov.: 0 AF XY: 0.00169 AC XY: 287AN XY: 170110
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0292 AC: 2660AN: 90980Hom.: 119 Cov.: 0 AF XY: 0.0299 AC XY: 1288AN XY: 43036
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at