17-30249088-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000386.4(BLMH):c.1297G>A(p.Val433Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,110 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
BLMH
NM_000386.4 missense
NM_000386.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.43
Genes affected
BLMH (HGNC:1059): (bleomycin hydrolase) Bleomycin hydrolase (BMH) is a cytoplasmic cysteine peptidase that is highly conserved through evolution; however, the only known activity of the enzyme is metabolic inactivation of the glycopeptide bleomycin (BLM), an essential component of combination chemotherapy regimens for cancer. The protein contains the signature active site residues of the cysteine protease papain superfamily. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.099532455).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLMH | NM_000386.4 | c.1297G>A | p.Val433Met | missense_variant | 12/12 | ENST00000261714.11 | |
LOC105371720 | XR_001752824.2 | n.892-699C>T | intron_variant, non_coding_transcript_variant | ||||
LOC105371720 | XR_007065695.1 | n.756-699C>T | intron_variant, non_coding_transcript_variant | ||||
LOC105371720 | XR_007065698.1 | n.756-2986C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLMH | ENST00000261714.11 | c.1297G>A | p.Val433Met | missense_variant | 12/12 | 1 | NM_000386.4 | P1 | |
ENST00000577420.1 | n.61-2986C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
BLMH | ENST00000578795.1 | n.1196G>A | non_coding_transcript_exon_variant | 1/1 | |||||
BLMH | ENST00000578090.5 | c.*971G>A | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251336Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135824
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461816Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727212
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74454
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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 | Sep 14, 2023 | The c.1297G>A (p.V433M) alteration is located in exon 12 (coding exon 12) of the BLMH gene. This alteration results from a G to A substitution at nucleotide position 1297, causing the valine (V) at amino acid position 433 to be replaced by a methionine (M). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at V429 (P = 0.0254);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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