Variant 1-169376656-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001320973.2(BLZF1):c.145A>C(p.Ser49Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000621 in 1,613,392 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 (★).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.54

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 0 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity GO45_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056455076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BLZF1	NM_001320973.2 linkuse as main transcript	c.145A>C	p.Ser49Arg	missense_variant	3/7	ENST00000367808.8
BLZF1	NM_003666.4 linkuse as main transcript	c.145A>C	p.Ser49Arg	missense_variant	3/8
BLZF1	NM_001320972.2 linkuse as main transcript	c.145A>C	p.Ser49Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLZF1	ENST00000367808.8 linkuse as main transcript	c.145A>C	p.Ser49Arg	missense_variant	3/7	1	NM_001320973.2	P1	Q9H2G9-1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000431

AC:

108

AN:

250722

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000848

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000652

AC:

952

AN:

1461234

Hom.:

Cov.:

AF XY:

0.000600

AC XY:

436

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000811

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000329

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000605

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000568

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

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

Dec 21, 2023

The c.145A>C (p.S49R) alteration is located in exon 3 (coding exon 2) of the BLZF1 gene. This alteration results from a A to C substitution at nucleotide position 145, causing the serine (S) at amino acid position 49 to be replaced by an arginine (R). 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

Benign

-0.36

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.054

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.53

T;T;.;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.056

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

M;M;M;.;.

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

D;N;N;D;N

REVEL

Benign

0.059

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Benign

0.096

T;T;T;T;T

Polyphen

0.96

D;B;B;.;.

Vest4

0.27

MutPred

0.27

Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);

MVP

0.63

MPC

0.15

ClinPred

0.12

GERP RS

4.1

Varity_R

0.12

gMVP

0.46

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