rs1366655332

Variant names:

• chr1-169378417-C-A
• NM_001320973.2:c.556C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-169378417-C-A
• chr1-169378417-C-G
• chr1-169378417-C-T

Variant summary

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

The NM_001320973.2(BLZF1):​c.556C>A​(p.Gln186Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q186E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 rank	MANE	Protein	UniProt
BLZF1	NM_001320973.2	c.556C>A	p.Gln186Lys	missense_variant	Exon 4 of 7	ENST00000367808.8	NP_001307902.1
BLZF1	NM_003666.4	c.556C>A	p.Gln186Lys	missense_variant	Exon 4 of 8		NP_003657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLZF1	ENST00000367808.8	c.556C>A	p.Gln186Lys	missense_variant	Exon 4 of 7	1	NM_001320973.2	ENSP00000356782.3
BLZF1	ENST00000329281.6	c.556C>A	p.Gln186Lys	missense_variant	Exon 4 of 8	1		ENSP00000327541.2
BLZF1	ENST00000426663.1	c.556C>A	p.Gln186Lys	missense_variant	Exon 4 of 5	3		ENSP00000404408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460948 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726796

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.27
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.78	P;P;.
Vest4		0.64
MutPred		0.64		Gain of ubiquitination at Q186 (P = 0.023);Gain of ubiquitination at Q186 (P = 0.023);Gain of ubiquitination at Q186 (P = 0.023);
MVP		0.53
MPC		0.45
ClinPred		0.95	D
GERP RS		6.2
Varity_R		0.30
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-169347655;