chr19-58563286-T-C

Variant names:

• chr19-58563286-T-C
• rs4756
• NM_198055.2:c.991A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198055.2(MZF1):​c.991A>G​(p.Ile331Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,605,748 control chromosomes in the GnomAD database, including 56,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (11313 hom., cov: 33)
  • Exomes 𝑓: 0.24 (45253 hom.)
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1531072E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MZF1	NM_198055.2	MANE Select	c.991A>G	p.Ile331Val	missense	Exon 6 of 6	NP_932172.1
	MZF1	NM_003422.3		c.991A>G	p.Ile331Val	missense	Exon 6 of 6	NP_003413.2
	MZF1	NM_001267033.2		c.773-26A>G		intron	N/A	NP_001253962.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MZF1	ENST00000215057.7	TSL:1 MANE Select	c.991A>G	p.Ile331Val	missense	Exon 6 of 6	ENSP00000215057.1
	MZF1	ENST00000599369.5	TSL:1	c.991A>G	p.Ile331Val	missense	Exon 6 of 6	ENSP00000469493.1
	MZF1	ENST00000594234.5	TSL:1	c.773-26A>G		intron	N/A	ENSP00000469378.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52240 AN: 151968 Hom.: 11286 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.310

GnomAD2 exomes AF: 0.272 AC: 63022 AN: 231626 AF XY: 0.267

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.152

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.239 AC: 346979 AN: 1453662 Hom.: 45253 Cov.: 34 AF XY: 0.240 AC XY: 173500 AN XY: 722514

African (AFR) AF: 0.640 AC: 21342 AN: 33326

American (AMR) AF: 0.340 AC: 14807 AN: 43552

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6417 AN: 25932

East Asian (EAS) AF: 0.160 AC: 6325 AN: 39430

South Asian (SAS) AF: 0.308 AC: 26276 AN: 85450

European-Finnish (FIN) AF: 0.239 AC: 12305 AN: 51552

Middle Eastern (MID) AF: 0.352 AC: 2017 AN: 5732

European-Non Finnish (NFE) AF: 0.218 AC: 241743 AN: 1108706

Other (OTH) AF: 0.263 AC: 15747 AN: 59982

GnomAD4 genome AF: 0.344 AC: 52324 AN: 152086 Hom.: 11313 Cov.: 33 AF XY: 0.340 AC XY: 25285 AN XY: 74362

African (AFR) AF: 0.617 AC: 25597 AN: 41500

American (AMR) AF: 0.325 AC: 4964 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.162 AC: 835 AN: 5162

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4826

European-Finnish (FIN) AF: 0.229 AC: 2427 AN: 10582

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15212 AN: 67942

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.246 Hom.: 6677

Bravo AF: 0.365

TwinsUK AF: 0.219 AC: 811

ALSPAC AF: 0.211 AC: 812

ESP6500AA AF: 0.610 AC: 2678

ESP6500EA AF: 0.214 AC: 1841

ExAC AF: 0.269 AC: 32402

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.76
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00059	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.51
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.029
Sift	Benign	0.58	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.0020
MPC		0.050
ClinPred		0.0033	T
GERP RS		2.5
La Branchor		0.89
Varity_R		0.027
gMVP		0.048
Mutation Taster		=100/0	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: rs4756; hg19: chr19-59074653; COSMIC: COSV53041681; COSMIC: COSV53041681;