Variant chr1-169378396-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320973.2(BLZF1):c.535C>T(p.Arg179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLZF1	NM_001320973.2 linkuse as main transcript	c.535C>T	p.Arg179Cys	missense_variant	4/7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4 linkuse as main transcript	c.535C>T	p.Arg179Cys	missense_variant	4/8		NP_003657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8 linkuse as main transcript	c.535C>T	p.Arg179Cys	missense_variant	4/7	1	NM_001320973.2	ENSP00000356782	P1	Q9H2G9-1
BLZF1	ENST00000329281.6 linkuse as main transcript	c.535C>T	p.Arg179Cys	missense_variant	4/8	1		ENSP00000327541	P1	Q9H2G9-1
BLZF1	ENST00000426663.1 linkuse as main transcript	c.535C>T	p.Arg179Cys	missense_variant	4/5	3		ENSP00000404408

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251100

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460900

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Apr 12, 2023

The c.535C>T (p.R179C) alteration is located in exon 4 (coding exon 3) of the BLZF1 gene. This alteration results from a C to T substitution at nucleotide position 535, causing the arginine (R) at amino acid position 179 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;.;D

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.074

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.89

P;P;.

Vest4

0.90

MVP

0.32

MPC

0.17

ClinPred

0.90

GERP RS

6.2

Varity_R

0.31

gMVP

0.44

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

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