NM_006969.5:c.143-287C>A

Variant names:

• chr19-52801989-G-T
• rs12461390
• NM_006969.5:c.143-287C>A

Variant summary

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

The NM_006969.5(ZNF28):​c.143-287C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,072 control chromosomes in the GnomAD database, including 1,062 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 0.089 (1062 hom., cov: 33)
• Consequence: ZNF28 NM_006969.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 5 publications found

Genes affected

ZNF28 (HGNC:13073): (zinc finger protein 28) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF600 (HGNC:30951): (zinc finger protein 600) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006969.5. 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
	ZNF28	NM_006969.5	MANE Select	c.143-287C>A		intron	N/A	NP_008900.3	P17035-1
	ZNF28	NM_001369763.1		c.134-287C>A		intron	N/A	NP_001356692.1
	ZNF28	NM_001369764.1		c.143-329C>A		intron	N/A	NP_001356693.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF28	ENST00000457749.7	TSL:1 MANE Select	c.143-287C>A		intron	N/A	ENSP00000397693.2	P17035-1
	ZNF28	ENST00000868404.1		c.143-329C>A		intron	N/A	ENSP00000538463.1
	ZNF28	ENST00000438150.2	TSL:2	c.-17-287C>A		intron	N/A	ENSP00000412143.2	P17035-2

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13446 AN: 151954 Hom.: 1057 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0725

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0886 AC: 13473 AN: 152072 Hom.: 1062 Cov.: 33 AF XY: 0.0893 AC XY: 6635 AN XY: 74340

African (AFR) AF: 0.190 AC: 7876 AN: 41446

American (AMR) AF: 0.107 AC: 1635 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.0815 AC: 421 AN: 5168

South Asian (SAS) AF: 0.194 AC: 936 AN: 4820

European-Finnish (FIN) AF: 0.0104 AC: 110 AN: 10570

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0320 AC: 2173 AN: 68006

Other (OTH) AF: 0.0764 AC: 161 AN: 2106

Alfa AF: 0.0664 Hom.: 223

Bravo AF: 0.0971

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.42
PhyloP100		0.042
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: rs12461390; hg19: chr19-53305242;