17-30249058-T-A

Variant names:

• chr17-30249058-T-A
• rs1050565
• NM_000386.4:c.1327A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000386.4(BLMH):​c.1327A>T​(p.Ile443Phe) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I443V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BLMH NM_000386.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

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]

ENSG00000266120 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17091131).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	NM_000386.4	MANE Select	c.1327A>T	p.Ile443Phe	missense	Exon 12 of 12	NP_000377.1	Q13867

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	ENST00000261714.11	TSL:1 MANE Select	c.1327A>T	p.Ile443Phe	missense	Exon 12 of 12	ENSP00000261714.6	Q13867
	BLMH	ENST00000935069.1		c.1420A>T	p.Ile474Phe	missense	Exon 13 of 13	ENSP00000605128.1
	BLMH	ENST00000935072.1		c.1207A>T	p.Ile403Phe	missense	Exon 11 of 11	ENSP00000605131.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.042
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.033	D
Polyphen		0.010	B
Vest4		0.13
MutPred		0.40		Loss of catalytic residue at P445 (P = 0.0271)
MVP		0.21
MPC		0.45
ClinPred		0.50	D
GERP RS		1.5
Varity_R		0.43
gMVP		0.56

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

Other links and lift over

dbSNP: rs1050565; hg19: chr17-28576076;