rs2043336

Variant names:

• chr19-2915740-T-A
• rs2043336
• NM_173480.3:c.130+92T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000253392 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF57	NM_173480.3	c.130+92T>A		intron_variant	Intron 2 of 3	ENST00000306908.10	NP_775751.1
ZNF57	NM_001319083.2	c.34+92T>A		intron_variant	Intron 2 of 3		NP_001306012.1
ZNF57	XM_011527682.3	c.34+92T>A		intron_variant	Intron 2 of 3		XP_011525984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10	c.130+92T>A		intron_variant	Intron 2 of 3	1	NM_173480.3	ENSP00000303696.5

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

GnomAD2 exomes AF: 0.843 AC: 209087 AN: 248012 AF XY: 0.843

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 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

African (AFR) AF: 0.757 AC: 24936 AN: 32934

American (AMR) AF: 0.858 AC: 38036 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 19762 AN: 25866

East Asian (EAS) AF: 0.747 AC: 29427 AN: 39396

South Asian (SAS) AF: 0.811 AC: 69409 AN: 85532

European-Finnish (FIN) AF: 0.896 AC: 47250 AN: 52730

Middle Eastern (MID) AF: 0.805 AC: 4597 AN: 5710

European-Non Finnish (NFE) AF: 0.881 AC: 961103 AN: 1091206

Other (OTH) AF: 0.837 AC: 49812 AN: 59498

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

African (AFR) AF: 0.769 AC: 31937 AN: 41510

American (AMR) AF: 0.845 AC: 12923 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2617 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3607 AN: 5174

South Asian (SAS) AF: 0.802 AC: 3861 AN: 4816

European-Finnish (FIN) AF: 0.897 AC: 9514 AN: 10612

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60039 AN: 68030

Other (OTH) AF: 0.820 AC: 1736 AN: 2116

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
PhyloP100		-1.8
GERP RS		-3.2
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2043336; hg19: chr19-2915738;