1-169387022-C-T

Variant names:

• chr1-169387022-C-T
• rs369740623
• NM_001320973.2:c.1043C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320973.2(BLZF1):​c.1043C>T​(p.Thr348Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,457,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. T348N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12860346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	NM_001320973.2	MANE Select	c.1043C>T	p.Thr348Ile	missense	Exon 7 of 7	NP_001307902.1	Q9H2G9-1
	BLZF1	NM_003666.4		c.1043C>T	p.Thr348Ile	missense	Exon 7 of 8	NP_003657.1	Q9H2G9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	ENST00000367808.8	TSL:1 MANE Select	c.1043C>T	p.Thr348Ile	missense	Exon 7 of 7	ENSP00000356782.3	Q9H2G9-1
	BLZF1	ENST00000329281.6	TSL:1	c.1043C>T	p.Thr348Ile	missense	Exon 7 of 8	ENSP00000327541.2	Q9H2G9-1
	BLZF1	ENST00000899417.1		c.1094C>T	p.Thr365Ile	missense	Exon 7 of 7	ENSP00000569476.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 248328 AF XY: 0.0000447

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1457650 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 725254

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.00 AC: 0 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 85516

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1110308

Other (OTH) AF: 0.00 AC: 0 AN: 60236

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.075
Sift	Benign	0.066	T
Sift4G	Uncertain	0.028	D
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.26		Loss of phosphorylation at T348 (P = 0.0375)
MVP		0.63
MPC		0.13
ClinPred		0.26	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.093
gMVP		0.38
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs369740623; hg19: chr1-169356260; COSMIC: COSV104536058;