chr6-2948469-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004568.6(SERPINB6):c.960T>G(p.Phe320Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SERPINB6
NM_004568.6 missense
NM_004568.6 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: -0.144
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB6 | NM_004568.6 | c.960T>G | p.Phe320Leu | missense_variant | 7/7 | ENST00000380539.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB6 | ENST00000380539.7 | c.960T>G | p.Phe320Leu | missense_variant | 7/7 | 3 | NM_004568.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727244
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.960T>G (p.F320L) alteration is located in exon 7 (coding exon 6) of the SERPINB6 gene. This alteration results from a T to G substitution at nucleotide position 960, causing the phenylalanine (F) at amino acid position 320 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
D;D;D;D;D;D;D;T;T;.;D;D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;M;M;.;.;.;M;M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;.;D;.;.;.;.;.;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.;D;.;.;.;.;.;D;.
Sift4G
Uncertain
D;D;D;D;.;D;.;D;.;.;.;D;.
Polyphen
B;B;B;B;B;B;B;.;.;.;B;B;.
Vest4
MutPred
Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);.;.;.;Loss of catalytic residue at F320 (P = 0.0427);Loss of catalytic residue at F320 (P = 0.0427);.;
MVP
MPC
0.34
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at