19-58563062-C-T

Variant names:

• chr19-58563062-C-T
• rs2228162
• NM_198055.2:c.1215G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_198055.2(MZF1):​c.1215G>A​(p.Thr405Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,602,794 control chromosomes in the GnomAD database, including 9,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (3353 hom., cov: 34)
  • Exomes 𝑓: 0.060 (5675 hom.)
• Consequence: MZF1 NM_198055.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 13 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

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.1215G>A	p.Thr405Thr	synonymous	Exon 6 of 6	NP_932172.1	P28698-1
	MZF1	NM_003422.3		c.1215G>A	p.Thr405Thr	synonymous	Exon 6 of 6	NP_003413.2
	MZF1	NM_001267033.2		c.*98G>A		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.1215G>A	p.Thr405Thr	synonymous	Exon 6 of 6	ENSP00000215057.1	P28698-1
	MZF1	ENST00000599369.5	TSL:1	c.1215G>A	p.Thr405Thr	synonymous	Exon 6 of 6	ENSP00000469493.1	P28698-1
	MZF1	ENST00000594234.5	TSL:1	c.*98G>A		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22677 AN: 152122 Hom.: 3345 Cov.: 34

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.104 AC: 23849 AN: 229974 AF XY: 0.0930

Gnomad AFR exome AF: 0.397

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.0441

Gnomad EAS exome AF: 0.0909

Gnomad FIN exome AF: 0.0428

Gnomad NFE exome AF: 0.0396

Gnomad OTH exome AF: 0.0792

GnomAD4 exome AF: 0.0597 AC: 86583 AN: 1450554 Hom.: 5675 Cov.: 32 AF XY: 0.0600 AC XY: 43331 AN XY: 721938

African (AFR) AF: 0.396 AC: 13234 AN: 33438

American (AMR) AF: 0.204 AC: 9064 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.0440 AC: 1148 AN: 26072

East Asian (EAS) AF: 0.109 AC: 4314 AN: 39666

South Asian (SAS) AF: 0.123 AC: 10624 AN: 86122

European-Finnish (FIN) AF: 0.0446 AC: 1938 AN: 43442

Middle Eastern (MID) AF: 0.0722 AC: 411 AN: 5696

European-Non Finnish (NFE) AF: 0.0371 AC: 41254 AN: 1111376

Other (OTH) AF: 0.0763 AC: 4596 AN: 60232

GnomAD4 genome AF: 0.149 AC: 22715 AN: 152240 Hom.: 3353 Cov.: 34 AF XY: 0.146 AC XY: 10899 AN XY: 74446

African (AFR) AF: 0.378 AC: 15677 AN: 41514

American (AMR) AF: 0.155 AC: 2377 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.102 AC: 529 AN: 5168

South Asian (SAS) AF: 0.119 AC: 575 AN: 4832

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2724 AN: 68014

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.0500 Hom.: 182

Bravo AF: 0.170

Asia WGS AF: 0.152 AC: 529 AN: 3478

EpiCase AF: 0.0415

EpiControl AF: 0.0407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.3
DANN	Benign	0.96
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs2228162; hg19: chr19-59074429; COSMIC: COSV53042204; COSMIC: COSV53042204;