chr19-57808847-A-T

Variant names:

• chr19-57808847-A-T
• rs372934566
• NM_024762.3:c.417T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024762.3(ZNF552):​c.417T>A​(p.Asn139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ZNF552 NM_024762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.23
• Publications: 0 publications found

Genes affected

ZNF552 (HGNC:26135): (zinc finger protein 552) 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]

ZNF586 (HGNC:25949): (zinc finger protein 586) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025311649).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024762.3. 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
	ZNF552	NM_024762.3	MANE Select	c.417T>A	p.Asn139Lys	missense	Exon 3 of 3	NP_079038.2	Q9H707

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF552	ENST00000391701.1	TSL:2 MANE Select	c.417T>A	p.Asn139Lys	missense	Exon 3 of 3	ENSP00000375582.1	Q9H707
	ZNF586	ENST00000598885.5	TSL:4	c.164-5579A>T		intron	N/A	ENSP00000470397.1	M0QZ99
	ZNF552	ENST00000594473.1	TSL:2	c.109+4447T>A		intron	N/A	ENSP00000472459.1	M0R2C3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151878 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251378 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151878 Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3 AN XY: 74144

African (AFR) AF: 0.00 AC: 0 AN: 41308

American (AMR) AF: 0.0000657 AC: 1 AN: 15232

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

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	Benign	0.16
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.012
DANN	Benign	0.26
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.066	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-3.2
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.046
MutPred		0.48		Gain of methylation at N139 (P = 0.0044)
MVP		0.099
MPC		1.2
ClinPred		0.079	T
GERP RS		-3.9
Varity_R		0.037
gMVP		0.022
Mutation Taster		=97/3	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: rs372934566; hg19: chr19-58320215;