Variant 1-169376813-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001320973.2(BLZF1):c.302C>A(p.Ser101Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,613,364 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S101F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004964322).

BP6

Variant 1-169376813-C-A is Benign according to our data. Variant chr1-169376813-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 789949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLZF1	NM_001320973.2 link	c.302C>A	p.Ser101Tyr	missense_variant	3/7	ENST00000367808.8	NP_001307902.1	Q9H2G9-1
BLZF1	NM_003666.4 link	c.302C>A	p.Ser101Tyr	missense_variant	3/8		NP_003657.1	Q9H2G9-1
BLZF1	NM_001320972.2 link	c.302C>A	p.Ser101Tyr	missense_variant	3/3		NP_001307901.1	Q9H2G9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8 link	c.302C>A	p.Ser101Tyr	missense_variant	3/7	1	NM_001320973.2	ENSP00000356782.3		Q9H2G9-1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000579

AC:

145

AN:

250468

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00668

Gnomad AMR exome

AF:

0.000754

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:

0.0000265

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000233

AC:

341

AN:

1461226

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00646

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00197

AC:

299

AN:

152138

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

141

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.00226

ESP6500AA

AF:

0.00795

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000782

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

.;T;T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T;.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.4

M;M;M;.;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.7

D;N;N;D;N

REVEL

Benign

0.068

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Benign

0.078

T;T;T;T;T

Polyphen

0.92

P;P;P;.;.

Vest4

0.34

MVP

0.51

MPC

0.42

ClinPred

0.041

GERP RS

5.1

Varity_R

0.23

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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