17-30291332-T-G

Variant names:

• chr17-30291332-T-G
• rs143544764
• NM_000386.4:c.190A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000386.4(BLMH):​c.190A>C​(p.Ile64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLMH NM_000386.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

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]

ACMG classification

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=0.36430973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLMH	NM_000386.4	c.190A>C	p.Ile64Leu	missense_variant	Exon 2 of 12	ENST00000261714.11	NP_000377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.190A>C	p.Ile64Leu	missense_variant	Exon 2 of 12	1	NM_000386.4	ENSP00000261714.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.80	N;.
REVEL	Benign	0.10
Sift	Benign	0.079	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.0	B;.
Vest4		0.44
MutPred		0.83		Loss of methylation at K62 (P = 0.0598);Loss of methylation at K62 (P = 0.0598);
MVP		0.50
MPC		0.27
ClinPred		0.20	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143544764; hg19: chr17-28618350;