Variant chr1-169378397-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320973.2(BLZF1):c.536G>A(p.Arg179His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,612,784 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R179C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.27

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20119119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLZF1	NM_001320973.2 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	4/7	ENST00000367808.8
BLZF1	NM_003666.4 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLZF1	ENST00000367808.8 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	4/7	1	NM_001320973.2	P1	Q9H2G9-1
BLZF1	ENST00000329281.6 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	4/8	1		P1	Q9H2G9-1
BLZF1	ENST00000426663.1 linkuse as main transcript	c.536G>A	p.Arg179His	missense_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

251102

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1460892

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00164

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000171

AC:

AN:

151892

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

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

Jan 29, 2024

The c.536G>A (p.R179H) alteration is located in exon 4 (coding exon 3) of the BLZF1 gene. This alteration results from a G to A substitution at nucleotide position 536, causing the arginine (R) at amino acid position 179 to be replaced by a histidine (H). 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

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

T;T;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.86

MVP

0.39

MPC

0.20

ClinPred

0.12

GERP RS

6.2

Varity_R

0.18

gMVP

0.35

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