rs143882259

Variant names:

• chr1-169376813-C-A
• rs143882259
• NM_001320973.2:c.302C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-169376813-C-A
• chr1-169376813-C-G
• chr1-169376813-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.18
• Publications: 4 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: Benign. The variant received -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 VariationId is 789949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.302C>A	p.Ser101Tyr	missense	Exon 3 of 7	NP_001307902.1	Q9H2G9-1
	BLZF1	NM_003666.4		c.302C>A	p.Ser101Tyr	missense	Exon 3 of 8	NP_003657.1	Q9H2G9-1
	BLZF1	NM_001320972.2		c.302C>A	p.Ser101Tyr	missense	Exon 3 of 3	NP_001307901.1	Q9H2G9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	ENST00000367808.8	TSL:1 MANE Select	c.302C>A	p.Ser101Tyr	missense	Exon 3 of 7	ENSP00000356782.3	Q9H2G9-1
	BLZF1	ENST00000329281.6	TSL:1	c.302C>A	p.Ser101Tyr	missense	Exon 3 of 8	ENSP00000327541.2	Q9H2G9-1
	BLZF1	ENST00000367807.7	TSL:1	c.302C>A	p.Ser101Tyr	missense	Exon 3 of 3	ENSP00000356781.3	Q9H2G9-2

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 299 AN: 152020 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000579 AC: 145 AN: 250468 AF XY: 0.000428

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 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.: 2 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 726920

African (AFR) AF: 0.00646 AC: 216 AN: 33454

American (AMR) AF: 0.000716 AC: 32 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111606

Other (OTH) AF: 0.000563 AC: 34 AN: 60374

GnomAD4 genome AF: 0.00197 AC: 299 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00190 AC XY: 141 AN XY: 74394

African (AFR) AF: 0.00686 AC: 285 AN: 41522

American (AMR) AF: 0.000656 AC: 10 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67960

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000625 Hom.: 0

Bravo AF: 0.00226

ESP6500AA AF: 0.00795 AC: 35

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000782 AC: 95

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.2
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.068
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.078	T
Polyphen		0.92	P
Vest4		0.34
MVP		0.51
MPC		0.42
ClinPred		0.041	T
GERP RS		5.1
Varity_R		0.23
gMVP		0.20
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs143882259; hg19: chr1-169346051;