rs4756

Positions:

• chr19-58563286-T-C
• chr19-58563286-T-G

Variant summary

Our verdict is Benign. Variant got -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MZF1	NM_198055.2	c.991A>G	p.Ile331Val	missense_variant	6/6	ENST00000215057.7
MZF1-AS1	NR_027334.2	n.224+3877T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MZF1	ENST00000215057.7	c.991A>G	p.Ile331Val	missense_variant	6/6	1	NM_198055.2	P1
MZF1-AS1	ENST00000600534.1	n.185+3877T>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.272 AC: 63022 AN: 231626 Hom.: 9671 AF XY: 0.267 AC XY: 33803 AN XY: 126714

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 SAS exome AF: 0.309

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

Gnomad4 AFR exome AF: 0.640

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.263

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

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.311

Alfa AF: 0.243 Hom.: 4838

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 v4.3

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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.010	N;.
REVEL	Benign	0.029
Sift	Benign	0.58	T;.
Sift4G	Benign	0.36	T;T
Polyphen		0.0	B;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4756; hg19: chr19-59074653; COSMIC: COSV53041681; COSMIC: COSV53041681;