rs372310785

Variant names:

• chr17-30272760-G-A
• rs372310785
• NM_000386.4:c.941C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000386.4(BLMH):​c.941C>T​(p.Ala314Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000409 in 1,614,138 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A314S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: BLMH NM_000386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1425766).

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.941C>T	p.Ala314Val	missense	Exon 8 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.941C>T	p.Ala314Val	missense	Exon 8 of 12	ENSP00000261714.6	Q13867
	BLMH	ENST00000935069.1		c.941C>T	p.Ala314Val	missense	Exon 8 of 13	ENSP00000605128.1
	BLMH	ENST00000935072.1		c.941C>T	p.Ala314Val	missense	Exon 8 of 11	ENSP00000605131.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251404 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727238

African (AFR) AF: 0.000627 AC: 21 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74454

African (AFR) AF: 0.000843 AC: 35 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000242

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		6.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Benign	0.23	T
Polyphen		0.10	B
Vest4		0.42
MVP		0.58
MPC		0.28
ClinPred		0.16	T
GERP RS		5.7
Varity_R		0.56
gMVP		0.67
Mutation Taster		=61/39	polymorphism

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: rs372310785; hg19: chr17-28599778;