19-58562077-C-A

Variant names:

• chr19-58562077-C-A
• rs377592261
• NM_198055.2:c.2200G>T

Variant summary

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

The NM_198055.2(MZF1):​c.2200G>T​(p.Glu734*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MZF1 NM_198055.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 0 publications found

Genes affected

MZF1 (HGNC:13108): (myeloid zinc finger 1) Enables DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MZF1-AS1 (HGNC:51271): (MZF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198055.2. 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
	MZF1	NM_198055.2	MANE Select	c.2200G>T	p.Glu734*	stop_gained	Exon 6 of 6	NP_932172.1	P28698-1
	MZF1	NM_003422.3		c.2200G>T	p.Glu734*	stop_gained	Exon 6 of 6	NP_003413.2
	MZF1	NM_001267033.2		c.*1083G>T		3_prime_UTR	Exon 6 of 6	NP_001253962.1	P28698-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MZF1	ENST00000215057.7	TSL:1 MANE Select	c.2200G>T	p.Glu734*	stop_gained	Exon 6 of 6	ENSP00000215057.1	P28698-1
	MZF1	ENST00000599369.5	TSL:1	c.2200G>T	p.Glu734*	stop_gained	Exon 6 of 6	ENSP00000469493.1	P28698-1
	MZF1	ENST00000594234.5	TSL:1	c.*1083G>T		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405622 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 694824

African (AFR) AF: 0.00 AC: 0 AN: 32114

American (AMR) AF: 0.00 AC: 0 AN: 36268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.0000273 AC: 1 AN: 36582

South Asian (SAS) AF: 0.00 AC: 0 AN: 80440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084836

Other (OTH) AF: 0.00 AC: 0 AN: 58394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	35
DANN	Uncertain	0.98
Eigen	Benign	0.17
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.20	N
PhyloP100		-0.23
Vest4		0.49
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=166/34	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: rs377592261; hg19: chr19-59073444;