19-7083618-A-G

Variant names:

• chr19-7083618-A-G
• rs966591
• NM_024341.3:c.1167A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024341.3(ZNF557):​c.1167A>G​(p.Ser389Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,586 control chromosomes in the GnomAD database, including 133,439 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 0.43 (14449 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118990 hom.)
• Consequence: ZNF557 NM_024341.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 23 publications found

Genes affected

ZNF557 (HGNC:28632): (zinc finger protein 557) 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]

ENSG00000301807 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-2.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF557	NM_024341.3	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 8 of 8	ENST00000252840.11	NP_077317.2
ZNF557	NM_001044387.2	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 8 of 8		NP_001037852.1
ZNF557	NM_001044388.2	c.1146A>G	p.Ser382Ser	synonymous_variant	Exon 8 of 8		NP_001037853.1
ZNF557	XM_047439432.1	c.1146A>G	p.Ser382Ser	synonymous_variant	Exon 8 of 8		XP_047295388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF557	ENST00000252840.11	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 8 of 8	1	NM_024341.3	ENSP00000252840.5

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65710 AN: 151864 Hom.: 14442 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.410

GnomAD2 exomes AF: 0.415 AC: 103926 AN: 250146 AF XY: 0.411

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.550

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.402 AC: 587425 AN: 1461604 Hom.: 118990 Cov.: 53 AF XY: 0.400 AC XY: 291164 AN XY: 727124

African (AFR) AF: 0.517 AC: 17310 AN: 33476

American (AMR) AF: 0.415 AC: 18572 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 9747 AN: 26130

East Asian (EAS) AF: 0.525 AC: 20852 AN: 39696

South Asian (SAS) AF: 0.369 AC: 31837 AN: 86248

European-Finnish (FIN) AF: 0.423 AC: 22592 AN: 53394

Middle Eastern (MID) AF: 0.342 AC: 1973 AN: 5768

European-Non Finnish (NFE) AF: 0.396 AC: 440485 AN: 1111782

Other (OTH) AF: 0.398 AC: 24057 AN: 60388

GnomAD4 genome AF: 0.433 AC: 65752 AN: 151982 Hom.: 14449 Cov.: 32 AF XY: 0.432 AC XY: 32063 AN XY: 74274

African (AFR) AF: 0.510 AC: 21124 AN: 41452

American (AMR) AF: 0.402 AC: 6136 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3466

East Asian (EAS) AF: 0.538 AC: 2779 AN: 5164

South Asian (SAS) AF: 0.360 AC: 1733 AN: 4810

European-Finnish (FIN) AF: 0.412 AC: 4352 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27061 AN: 67966

Other (OTH) AF: 0.408 AC: 858 AN: 2104

Alfa AF: 0.406 Hom.: 54930

Bravo AF: 0.435

Asia WGS AF: 0.423 AC: 1470 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.36
PhyloP100		-2.7
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: rs966591; hg19: chr19-7083629; COSMIC: COSV53273945;