NM_198055.2:c.1584G>C

Variant names:

• chr19-58562693-C-G
• rs61731801
• NM_198055.2:c.1584G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_198055.2(MZF1):​c.1584G>C​(p.Leu528Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,385,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L528L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MZF1 NM_198055.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.

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.1584G>C	p.Leu528Leu	synonymous	Exon 6 of 6	NP_932172.1	P28698-1
	MZF1	NM_003422.3		c.1584G>C	p.Leu528Leu	synonymous	Exon 6 of 6	NP_003413.2
	MZF1	NM_001267033.2		c.*467G>C		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.1584G>C	p.Leu528Leu	synonymous	Exon 6 of 6	ENSP00000215057.1	P28698-1
	MZF1	ENST00000599369.5	TSL:1	c.1584G>C	p.Leu528Leu	synonymous	Exon 6 of 6	ENSP00000469493.1	P28698-1
	MZF1	ENST00000594234.5	TSL:1	c.*467G>C		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1385746 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684224

African (AFR) AF: 0.00 AC: 0 AN: 31698

American (AMR) AF: 0.00 AC: 0 AN: 35766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 35912

South Asian (SAS) AF: 0.00 AC: 0 AN: 79554

European-Finnish (FIN) AF: 0.0000580 AC: 2 AN: 34486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5206

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1080092

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.8
DANN	Benign	0.90
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs61731801; hg19: chr19-59074060;