chr19-52405974-C-T

Variant names:

• chr19-52405974-C-T
• rs141013163
• NM_032423.3:c.83C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032423.3(ZNF528):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,022 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (6 hom.)
• Consequence: ZNF528 NM_032423.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.706
• Publications: 4 publications found

Genes affected

ZNF528 (HGNC:29384): (zinc finger protein 528) 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015334696).
• BP6: Variant 19-52405974-C-T is Benign according to our data. Variant chr19-52405974-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 782628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032423.3. 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
	ZNF528	NM_032423.3	MANE Select	c.83C>T	p.Ala28Val	missense	Exon 5 of 7	NP_115799.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF528	ENST00000360465.8	TSL:1 MANE Select	c.83C>T	p.Ala28Val	missense	Exon 5 of 7	ENSP00000353652.3	Q3MIS6-1
	ZNF528	ENST00000862203.1		c.83C>T	p.Ala28Val	missense	Exon 4 of 6	ENSP00000532262.1
	ZNF528	ENST00000862204.1		c.83C>T	p.Ala28Val	missense	Exon 4 of 6	ENSP00000532263.1

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 305 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00200 AC: 503 AN: 251422 AF XY: 0.00219

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00280

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00277 AC: 4042 AN: 1459750 Hom.: 6 Cov.: 30 AF XY: 0.00279 AC XY: 2024 AN XY: 726146

African (AFR) AF: 0.000449 AC: 15 AN: 33438

American (AMR) AF: 0.00190 AC: 85 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00286 AC: 247 AN: 86250

European-Finnish (FIN) AF: 0.000470 AC: 25 AN: 53166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00318 AC: 3530 AN: 1110514

Other (OTH) AF: 0.00232 AC: 140 AN: 60236

GnomAD4 genome AF: 0.00200 AC: 305 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74456

African (AFR) AF: 0.000722 AC: 30 AN: 41560

American (AMR) AF: 0.00392 AC: 60 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4816

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00291 AC: 198 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00212 Hom.: 1

Bravo AF: 0.00210

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00208 AC: 253

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00338

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.056	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.71
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.10
Sift	Benign	0.22	T
Sift4G	Uncertain	0.029	D
Polyphen		0.81	P
Vest4		0.21
MVP		0.33
MPC		0.058
ClinPred		0.016	T
GERP RS		2.1
PromoterAI		-0.027	Neutral
Varity_R		0.058
gMVP		0.047
Mutation Taster		=100/0	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: rs141013163; hg19: chr19-52909227; COSMIC: COSV64621362; COSMIC: COSV64621362;