rs727505227
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004568.6(SERPINB6):c.1128G>A(p.Pro376Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
SERPINB6
NM_004568.6 synonymous
NM_004568.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.74
Genes affected
SERPINB6 (HGNC:8950): (serpin family B member 6) The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 6-2948301-C-T is Benign according to our data. Variant chr6-2948301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 179927.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-2948301-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-6.74 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINB6 | NM_004568.6 | c.1128G>A | p.Pro376Pro | synonymous_variant | 7/7 | ENST00000380539.7 | NP_004559.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERPINB6 | ENST00000380539.7 | c.1128G>A | p.Pro376Pro | synonymous_variant | 7/7 | 3 | NM_004568.6 | ENSP00000369912.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251120Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135746
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461182Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 726872
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 11, 2014 | Pro376Pro in exon 8 of SERPINB6: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at