rs324125

Variant names:

• chr19-52384029-A-G
• rs324125
• NM_001145434.2:c.449A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF880	NM_001145434.2	c.449A>G	p.Tyr150Cys	missense_variant	Exon 4 of 4	ENST00000422689.3	NP_001138906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF880	ENST00000422689.3	c.449A>G	p.Tyr150Cys	missense_variant	Exon 4 of 4	2	NM_001145434.2	ENSP00000406318.2
ZNF880	ENST00000424032.6	c.*191A>G		downstream_gene_variant		4		ENSP00000414470.2

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

GnomAD2 exomes AF: 0.127 AC: 20721 AN: 163008 AF XY: 0.126

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 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

African (AFR) AF: 0.248 AC: 7863 AN: 31658

American (AMR) AF: 0.0968 AC: 3469 AN: 35842

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4322 AN: 25212

East Asian (EAS) AF: 0.138 AC: 4989 AN: 36042

South Asian (SAS) AF: 0.0874 AC: 6975 AN: 79808

European-Finnish (FIN) AF: 0.120 AC: 5972 AN: 49656

Middle Eastern (MID) AF: 0.135 AC: 767 AN: 5698

European-Non Finnish (NFE) AF: 0.132 AC: 142486 AN: 1081084

Other (OTH) AF: 0.138 AC: 8047 AN: 58178

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

African (AFR) AF: 0.242 AC: 10025 AN: 41492

American (AMR) AF: 0.114 AC: 1737 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3472

East Asian (EAS) AF: 0.126 AC: 653 AN: 5182

South Asian (SAS) AF: 0.0888 AC: 429 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1307 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9371 AN: 68000

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.142 Hom.: 7655

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
PhyloP100		-0.22
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
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: rs324125; hg19: chr19-52887282; COSMIC: COSV69906983; COSMIC: COSV69906983;