Genetic Variant BLZF1:p.Ser101Cys (chr1-169376813-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001320973.2(BLZF1):c.302C>G(p.Ser101Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00182 in 1,613,348 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S101Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 3 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015164405).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLZF1	NM_001320973.2 link	c.302C>G	p.Ser101Cys	missense_variant	Exon 3 of 7	ENST00000367808.8	NP_001307902.1	Q9H2G9-1
BLZF1	NM_003666.4 link	c.302C>G	p.Ser101Cys	missense_variant	Exon 3 of 8		NP_003657.1	Q9H2G9-1
BLZF1	NM_001320972.2 link	c.302C>G	p.Ser101Cys	missense_variant	Exon 3 of 3		NP_001307901.1	Q9H2G9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8 link	c.302C>G	p.Ser101Cys	missense_variant	Exon 3 of 7	1	NM_001320973.2	ENSP00000356782.3		Q9H2G9-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00116

AC:

290

AN:

250468

Hom.:

AF XY:

0.00109

AC XY:

148

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000927

Gnomad NFE exome

AF:

0.00213

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00188

AC:

2753

AN:

1461212

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

1335

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000956

Gnomad4 NFE exome

AF:

0.00232

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

152136

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000625

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.00131

AC:

159

EpiCase

AF:

0.00186

EpiControl

AF:

0.00119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;T;T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

T;T;.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.4

M;M;M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

D;N;N;D;N

REVEL

Benign

0.098

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Benign

0.069

T;T;T;T;T

Polyphen

1.0

D;D;D;.;.

Vest4

0.34

MVP

0.48

MPC

0.43

ClinPred

0.039

GERP RS

5.1

Varity_R

0.15

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over