Variant chr1-169376966-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001320973.2(BLZF1):c.455G>T(p.Arg152Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,398 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: 0.0000021 ( 0 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

BLZF1 (HGNC:1065): (basic leucine zipper nuclear factor 1) Enables ubiquitin protein ligase binding activity. Acts upstream of or within Golgi organization and Golgi to plasma membrane protein transport. Located in Golgi apparatus and nucleoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

BLZF1 links:

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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=0.41272715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BLZF1	NM_001320973.2 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/8		NP_003657.1
BLZF1	NM_001320972.2 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/3		NP_001307901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/7	1	NM_001320973.2	ENSP00000356782	P1	Q9H2G9-1
BLZF1	ENST00000329281.6 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/8	1		ENSP00000327541	P1	Q9H2G9-1
BLZF1	ENST00000367807.7 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/3	1		ENSP00000356781		Q9H2G9-2
BLZF1	ENST00000426663.1 linkuse as main transcript	c.455G>T	p.Arg152Leu	missense_variant	3/5	3		ENSP00000404408

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248148

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460398

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

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

Feb 27, 2024

The c.455G>T (p.R152L) alteration is located in exon 3 (coding exon 2) of the BLZF1 gene. This alteration results from a G to T substitution at nucleotide position 455, causing the arginine (R) at amino acid position 152 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;.;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

M;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.2

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.024

D;T;T;T

Polyphen

1.0

D;P;P;.

Vest4

0.71

MutPred

0.37

Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);Loss of MoRF binding (P = 0.0047);

MVP

0.54

MPC

0.29

ClinPred

0.95

GERP RS

4.3

Varity_R

0.19

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over