chr19-17256566-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_031941.4(USHBP1):c.1375G>A(p.Glu459Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,850 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
USHBP1
NM_031941.4 missense
NM_031941.4 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 2.25
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.40440246).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USHBP1 | NM_031941.4 | c.1375G>A | p.Glu459Lys | missense_variant | 9/13 | ENST00000252597.8 | |
USHBP1 | NM_001321417.2 | c.1375G>A | p.Glu459Lys | missense_variant | 9/13 | ||
USHBP1 | NM_001297703.2 | c.1183G>A | p.Glu395Lys | missense_variant | 8/12 | ||
USHBP1 | NR_135632.2 | n.1616G>A | non_coding_transcript_exon_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USHBP1 | ENST00000252597.8 | c.1375G>A | p.Glu459Lys | missense_variant | 9/13 | 1 | NM_031941.4 | P1 | |
USHBP1 | ENST00000431146.6 | c.1183G>A | p.Glu395Lys | missense_variant | 8/12 | 2 | |||
USHBP1 | ENST00000324554.9 | c.*341G>A | 3_prime_UTR_variant, NMD_transcript_variant | 10/14 | 2 | ||||
USHBP1 | ENST00000597928.5 | c.*2495G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/12 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 exome
AF:
AC:
10
AN:
1461850
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727226
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
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ExAC
?
AF:
AC:
1
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 | Jun 06, 2022 | The c.1375G>A (p.E459K) alteration is located in exon 9 (coding exon 8) of the USHBP1 gene. This alteration results from a G to A substitution at nucleotide position 1375, causing the glutamic acid (E) at amino acid position 459 to be replaced by a lysine (K). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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