rs147792064
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004568.6(SERPINB6):c.996C>T(p.Ala332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,614,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 2 hom. )
Consequence
SERPINB6
NM_004568.6 synonymous
NM_004568.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.88
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 6-2948433-G-A is Benign according to our data. Variant chr6-2948433-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.88 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB6 | NM_004568.6 | c.996C>T | p.Ala332= | synonymous_variant | 7/7 | ENST00000380539.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB6 | ENST00000380539.7 | c.996C>T | p.Ala332= | synonymous_variant | 7/7 | 3 | NM_004568.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000741 AC: 186AN: 250864Hom.: 2 AF XY: 0.000678 AC XY: 92AN XY: 135718
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GnomAD4 exome AF: 0.000381 AC: 557AN: 1461870Hom.: 2 Cov.: 32 AF XY: 0.000366 AC XY: 266AN XY: 727238
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GnomAD4 genome ? AF: 0.000348 AC: 53AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74352
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 04, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 09, 2016 | p.Ala332Ala in exon 8 of SERPINB6: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 0.1% (65/66204) o f European chromosomes, including 1 homozygote, by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs147792064). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at