8-124976781-C-G

Variant names:

• chr8-124976781-C-G
• rs142684750
• NM_152412.3:c.513C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152412.3(ZNF572):​c.513C>G​(p.Asn171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: ZNF572 NM_152412.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.83
• Publications: 1 publications found

Genes affected

ZNF572 (HGNC:26758): (zinc finger protein 572) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007748246).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152412.3. 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
	ZNF572	NM_152412.3	MANE Select	c.513C>G	p.Asn171Lys	missense	Exon 3 of 3	NP_689625.2	Q7Z3I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF572	ENST00000319286.6	TSL:1 MANE Select	c.513C>G	p.Asn171Lys	missense	Exon 3 of 3	ENSP00000319305.5	Q7Z3I7
	ZNF572	ENST00000902451.1		c.513C>G	p.Asn171Lys	missense	Exon 3 of 3	ENSP00000572510.1
	ZNF572	ENST00000942607.1		c.513C>G	p.Asn171Lys	missense	Exon 3 of 3	ENSP00000612666.1

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000402 AC: 101 AN: 251236 AF XY: 0.000376

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000201 AC: 294 AN: 1461850 Hom.: 2 Cov.: 31 AF XY: 0.000176 AC XY: 128 AN XY: 727218

African (AFR) AF: 0.00105 AC: 35 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000117 AC: 130 AN: 1111996

Other (OTH) AF: 0.000546 AC: 33 AN: 60394

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74476

African (AFR) AF: 0.00137 AC: 57 AN: 41584

American (AMR) AF: 0.000915 AC: 14 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000774

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00063	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.80	N
PhyloP100		-1.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.031
Sift	Benign	0.17	T
Sift4G	Benign	0.58	T
Polyphen		0.22	B
Vest4		0.19
MutPred		0.32		Gain of methylation at N171 (P = 0.0017)
MVP		0.20
MPC		0.16
ClinPred		0.018	T
GERP RS		3.4
Varity_R		0.068
gMVP		0.034
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142684750; hg19: chr8-125989023;