1-169378417-C-G

Position:

• chr1-169378417-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320973.2(BLZF1):​c.556C>G​(p.Gln186Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLZF1	NM_001320973.2	c.556C>G	p.Gln186Glu	missense_variant	4/7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4	c.556C>G	p.Gln186Glu	missense_variant	4/8		NP_003657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8	c.556C>G	p.Gln186Glu	missense_variant	4/7	1	NM_001320973.2	ENSP00000356782	P1
BLZF1	ENST00000329281.6	c.556C>G	p.Gln186Glu	missense_variant	4/8	1		ENSP00000327541	P1
BLZF1	ENST00000426663.1	c.556C>G	p.Gln186Glu	missense_variant	4/5	3		ENSP00000404408

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.556C>G (p.Q186E) alteration is located in exon 4 (coding exon 3) of the BLZF1 gene. This alteration results from a C to G substitution at nucleotide position 556, causing the glutamine (Q) at amino acid position 186 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.00090	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;D;T
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.56	P;P;.
Vest4		0.63
MutPred		0.57		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.51
MPC		0.32
ClinPred		0.72	D
GERP RS		6.2
Varity_R		0.27
gMVP		0.29

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

Other links and lift over

dbSNP: rs1366655332; hg19: chr1-169347655;