19-58562737-C-T

Variant names:

• chr19-58562737-C-T
• rs150590904
• NM_198055.2:c.1540G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198055.2(MZF1):​c.1540G>A​(p.Gly514Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G514R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.40
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09772998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZF1	NM_198055.2	c.1540G>A	p.Gly514Ser	missense_variant	Exon 6 of 6	ENST00000215057.7	NP_932172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZF1	ENST00000215057.7	c.1540G>A	p.Gly514Ser	missense_variant	Exon 6 of 6	1	NM_198055.2	ENSP00000215057.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383980 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683206

African (AFR) AF: 0.00 AC: 0 AN: 31614

American (AMR) AF: 0.0000280 AC: 1 AN: 35736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 35804

South Asian (SAS) AF: 0.00 AC: 0 AN: 79530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079366

Other (OTH) AF: 0.00 AC: 0 AN: 57854

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.79	N;N
PhyloP100		-5.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.40	N;.
REVEL	Benign	0.042
Sift	Benign	0.12	T;.
Sift4G	Benign	0.61	T;T
Polyphen		0.28	B;B
Vest4		0.10
MutPred		0.25		Gain of disorder (P = 0.1018);Gain of disorder (P = 0.1018);
MVP		0.22
MPC		0.76
ClinPred		0.11	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.074
Mutation Taster		=98/2	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: rs150590904; hg19: chr19-59074104;