rs2043336

Positions:

• chr19-2915740-T-A
• chr19-2915740-T-C
• chr19-2915740-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173480.3(ZNF57):​c.130+92T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,589,416 control chromosomes in the GnomAD database, including 593,747 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 0.84 (53559 hom., cov: 33)
  • Exomes 𝑓: 0.87 (540188 hom.)
• Consequence: ZNF57 NM_173480.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.905119).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF57	NM_173480.3	c.130+92T>A		intron_variant		ENST00000306908.10
ZNF57	NM_001319083.2	c.34+92T>A		intron_variant
ZNF57	XM_011527682.3	c.34+92T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF57	ENST00000306908.10	c.130+92T>A		intron_variant		1	NM_173480.3	P1
	ENST00000654521.1	n.293-454A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127302 AN: 152106 Hom.: 53545 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.823

GnomAD3 exomes AF: 0.843 AC: 209087 AN: 248012 Hom.: 88583 AF XY: 0.843 AC XY: 113258 AN XY: 134318

Gnomad AFR exome AF: 0.771

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.698

Gnomad SAS exome AF: 0.805

Gnomad FIN exome AF: 0.897

Gnomad NFE exome AF: 0.879

Gnomad OTH exome AF: 0.844

GnomAD4 exome AF: 0.866 AC: 1244332 AN: 1437192 Hom.: 540188 Cov.: 23 AF XY: 0.864 AC XY: 618946 AN XY: 716352

Gnomad4 AFR exome AF: 0.757

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.747

Gnomad4 SAS exome AF: 0.811

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.881

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.837 AC: 127362 AN: 152224 Hom.: 53559 Cov.: 33 AF XY: 0.837 AC XY: 62302 AN XY: 74430

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.820

Alfa AF: 0.849 Hom.: 9713

Bravo AF: 0.827

TwinsUK AF: 0.877 AC: 3251

ALSPAC AF: 0.871 AC: 3355

ExAC AF: 0.842 AC: 102227

Asia WGS AF: 0.749 AC: 2604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.91	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.49
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
MutationTaster	Benign	1.0	P;P
GERP RS		-3.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2043336; hg19: chr19-2915738;