rs324125

Positions:

• chr19-52384029-A-G

Variant summary

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

The NM_001145434.2(ZNF880):​c.449A>G​(p.Tyr150Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,555,352 control chromosomes in the GnomAD database, including 14,987 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2191 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12796 hom.)
• Consequence: ZNF880 NM_001145434.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

Genes affected

ZNF880 (HGNC:37249): (zinc finger protein 880) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005609393).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF880	NM_001145434.2	c.449A>G	p.Tyr150Cys	missense_variant	4/4	ENST00000422689.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF880	ENST00000422689.3	c.449A>G	p.Tyr150Cys	missense_variant	4/4	2	NM_001145434.2	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24570 AN: 152056 Hom.: 2195 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.127 AC: 20721 AN: 163008 Hom.: 1419 AF XY: 0.126 AC XY: 10926 AN XY: 86560

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.0944

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.0889

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.132 AC: 184890 AN: 1403178 Hom.: 12796 Cov.: 41 AF XY: 0.131 AC XY: 90605 AN XY: 692726

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.0968

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0874

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.162 AC: 24584 AN: 152174 Hom.: 2191 Cov.: 33 AF XY: 0.158 AC XY: 11747 AN XY: 74400

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.158

Alfa AF: 0.137 Hom.: 3796

Bravo AF: 0.163

TwinsUK AF: 0.128 AC: 474

ALSPAC AF: 0.126 AC: 485

ESP6500AA AF: 0.236 AC: 327

ESP6500EA AF: 0.143 AC: 454

ExAC AF: 0.0867 AC: 9221

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.88
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.086	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.017
Sift	Benign	0.17	T
Sift4G	Benign	0.17	T
Polyphen		0.017	B
Vest4		0.040
MPC		0.21
ClinPred		0.00074	T
GERP RS		-2.9
Varity_R		0.042
gMVP		0.034

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: rs324125; hg19: chr19-52887282; COSMIC: COSV69906983; COSMIC: COSV69906983;