chr6-2948337-G-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004568.6(SERPINB6):c.1092C>A(p.Thr364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SERPINB6
NM_004568.6 synonymous
NM_004568.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0240
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 6-2948337-G-T is Benign according to our data. Variant chr6-2948337-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1120058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB6 | NM_004568.6 | c.1092C>A | p.Thr364= | synonymous_variant | 7/7 | ENST00000380539.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB6 | ENST00000380539.7 | c.1092C>A | p.Thr364= | synonymous_variant | 7/7 | 3 | NM_004568.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251330Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135844
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727210
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152254Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Apr 30, 2012 | Thr364Thr in Exon 08 of SERPINB6: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1/3738 African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 17, 2021 | - - |
Computational scores
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Name
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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