1-169387177-C-A

Variant names:

• chr1-169387177-C-A
• NM_001320973.2:c.1198C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320973.2(BLZF1):​c.1198C>A​(p.Leu400Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22479278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLZF1	NM_001320973.2	c.1198C>A	p.Leu400Ile	missense_variant	Exon 7 of 7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4	c.1198C>A	p.Leu400Ile	missense_variant	Exon 7 of 8		NP_003657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8	c.1198C>A	p.Leu400Ile	missense_variant	Exon 7 of 7	1	NM_001320973.2	ENSP00000356782.3
BLZF1	ENST00000329281.6	c.1198C>A	p.Leu400Ile	missense_variant	Exon 7 of 8	1		ENSP00000327541.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1198C>A (p.L400I) alteration is located in exon 7 (coding exon 6) of the BLZF1 gene. This alteration results from a C to A substitution at nucleotide position 1198, causing the leucine (L) at amino acid position 400 to be replaced by an isoleucine (I). 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	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.088
Sift	Benign	0.087	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.63	P;P
Vest4		0.48
MutPred		0.33		Loss of catalytic residue at L400 (P = 0.0674);Loss of catalytic residue at L400 (P = 0.0674);
MVP		0.24
MPC		0.15
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.097
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-169356415;