Variant 1-169376722-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001320973.2(BLZF1):c.211G>A(p.Glu71Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BLZF1
NM_001320973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2832913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLZF1	NM_001320973.2 link	c.211G>A	p.Glu71Lys	missense_variant	3/7	ENST00000367808.8	NP_001307902.1	Q9H2G9-1
BLZF1	NM_003666.4 link	c.211G>A	p.Glu71Lys	missense_variant	3/8		NP_003657.1	Q9H2G9-1
BLZF1	NM_001320972.2 link	c.211G>A	p.Glu71Lys	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.211G>A	p.Glu71Lys	missense_variant	3/7	1	NM_001320973.2	ENSP00000356782.3		Q9H2G9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250616

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 14, 2024

The c.211G>A (p.E71K) alteration is located in exon 3 (coding exon 2) of the BLZF1 gene. This alteration results from a G to A substitution at nucleotide position 211, causing the glutamic acid (E) at amino acid position 71 to be replaced by a lysine (K). 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

0.095

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

.;T;T;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.4

M;M;M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

D;N;N;D;N

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D;D;D;D

Sift4G

Uncertain

0.031

D;T;T;D;T

Polyphen

0.97

D;P;P;.;.

Vest4

0.26

MutPred

0.40

Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);Gain of MoRF binding (P = 0.003);

MVP

0.48

MPC

0.20

ClinPred

0.89

GERP RS

4.3

Varity_R

0.16

gMVP

0.25

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