rs3732782

chr3-114236317-T-G

Variant summary

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

The NM_007136.4(ZNF80):c.758A>C(p.Asp253Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,612,690 control chromosomes in the GnomAD database, including 339,067 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (36006 hom., cov: 33)
  • Exomes 𝑓: 0.64 (303061 hom.)
• Consequence: ZNF80 NM_007136.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

ZNF80 (HGNC:13155): (zinc finger protein 80) 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 act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. [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=1.0061316E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF80	NM_007136.4	c.758A>C	p.Asp253Ala	missense_variant	1/1	ENST00000482457.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF80	ENST00000482457.4	c.758A>C	p.Asp253Ala	missense_variant	1/1		NM_007136.4	P1
ZNF80	ENST00000308095.4	c.758A>C	p.Asp253Ala	missense_variant, NMD_transcript_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103828 AN: 151976 Hom.: 35958 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.695

GnomAD3 exomes AF: 0.652 AC: 163641 AN: 251122 Hom.: 53725 AF XY: 0.653 AC XY: 88608 AN XY: 135720

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.603

Gnomad ASJ exome AF: 0.739

Gnomad EAS exome AF: 0.531

Gnomad SAS exome AF: 0.705

Gnomad FIN exome AF: 0.678

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.657

GnomAD4 exome AF: 0.642 AC: 938420 AN: 1460594 Hom.: 303061 Cov.: 51 AF XY: 0.644 AC XY: 468234 AN XY: 726596

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.683 AC: 103935 AN: 152096 Hom.: 36006 Cov.: 33 AF XY: 0.684 AC XY: 50851 AN XY: 74326

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.694

Alfa AF: 0.654 Hom.: 51736

Bravo AF: 0.682

TwinsUK AF: 0.632 AC: 2343

ALSPAC AF: 0.626 AC: 2412

ESP6500AA AF: 0.799 AC: 3519

ESP6500EA AF: 0.644 AC: 5541

ExAC AF: 0.656 AC: 79656

Asia WGS AF: 0.640 AC: 2228 AN: 3478

EpiCase AF: 0.646

EpiControl AF: 0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.38
Dann	Benign	0.85
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0055	N
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	5.0	N;.
REVEL	Benign	0.029
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.024
MPC		0.13
ClinPred		0.00043	T
GERP RS		2.1
Varity_R		0.042
gMVP		0.013

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: rs3732782; hg19: chr3-113955164; COSMIC: COSV100351923; COSMIC: COSV100351923;