chr19-36547410-C-T

Variant names:

• chr19-36547410-C-T
• rs568515212
• NM_020951.5:c.1148G>A

Variant summary

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

The NM_020951.5(ZNF529):​c.1148G>A​(p.Arg383His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,613,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ZNF529 NM_020951.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.58
• Publications: 1 publications found

Genes affected

ZNF529 (HGNC:29328): (zinc finger protein 529) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13538954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020951.5. 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
	ZNF529	NM_020951.5	MANE Select	c.1148G>A	p.Arg383His	missense	Exon 5 of 5	NP_066002.3	Q6P280
	ZNF529	NM_001145649.2		c.1148G>A	p.Arg383His	missense	Exon 6 of 6	NP_001139121.1	Q6P280
	ZNF529	NM_001145650.2		c.1094G>A	p.Arg365His	missense	Exon 5 of 5	NP_001139122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF529	ENST00000591340.6	TSL:1 MANE Select	c.1148G>A	p.Arg383His	missense	Exon 5 of 5	ENSP00000465578.1	Q6P280
	ZNF529	ENST00000867184.1		c.1148G>A	p.Arg383His	missense	Exon 5 of 5	ENSP00000537243.1
	ZNF529	ENST00000867185.1		c.1148G>A	p.Arg383His	missense	Exon 5 of 5	ENSP00000537244.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151408 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249970 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461512 Hom.: 0 Cov.: 34 AF XY: 0.0000468 AC XY: 34 AN XY: 727034

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000447 AC: 2 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111788

Other (OTH) AF: 0.000166 AC: 10 AN: 60378

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151528 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74038

African (AFR) AF: 0.0000242 AC: 1 AN: 41314

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000775 Hom.: 0

Bravo AF: 0.0000302

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.32	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-6.6
PrimateAI	Uncertain	0.52	T
REVEL	Benign	0.082
Sift4G	Benign	0.18	T
Vest4		0.14
MVP		0.48
MPC		0.67
ClinPred		0.49	T
GERP RS		0.64
PromoterAI		-0.046	Neutral
Varity_R		0.034
gMVP		0.058
Mutation Taster		=99/1	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: rs568515212; hg19: chr19-37038312; COSMIC: COSV61899845; COSMIC: COSV61899845;