chr19-17250280-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_031941.4(USHBP1):c.2057T>A(p.Leu686Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,462 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: 0.0000014 ( 0 hom. )
Consequence
USHBP1
NM_031941.4 missense
NM_031941.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 1.58
Genes affected
USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USHBP1 | NM_031941.4 | c.2057T>A | p.Leu686Gln | missense_variant | 13/13 | ENST00000252597.8 | NP_114147.2 | |
USHBP1 | NM_001321417.2 | c.2057T>A | p.Leu686Gln | missense_variant | 13/13 | NP_001308346.1 | ||
USHBP1 | NM_001297703.2 | c.1865T>A | p.Leu622Gln | missense_variant | 12/12 | NP_001284632.1 | ||
USHBP1 | NR_135632.2 | n.2298T>A | non_coding_transcript_exon_variant | 14/14 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249864Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135418
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461296Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726946
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
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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 | Mar 31, 2023 | The c.2057T>A (p.L686Q) alteration is located in exon 13 (coding exon 12) of the USHBP1 gene. This alteration results from a T to A substitution at nucleotide position 2057, causing the leucine (L) at amino acid position 686 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
T;T
Polyphen
D;.
Vest4
MutPred
Loss of stability (P = 0.0429);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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