NM_007136.4:c.758A>C

Variant names:

• chr3-114236317-T-G
• rs3732782
• NM_007136.4:c.758A>C

Variant summary

Our verdict is Benign. The variant received -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. 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 0.68 (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
• Publications: 33 publications found

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]

ENSG00000241490 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007136.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF80	NM_007136.4	MANE Select	c.758A>C	p.Asp253Ala	missense	Exon 1 of 1	NP_009067.2	P51504

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF80	ENST00000482457.4	TSL:6 MANE Select	c.758A>C	p.Asp253Ala	missense	Exon 1 of 1	ENSP00000417192.3	P51504
	ZNF80	ENST00000308095.4	TSL:1	n.758A>C		non_coding_transcript_exon	Exon 1 of 2	ENSP00000309812.4	P51504
	ENSG00000241490	ENST00000493033.1	TSL:2	n.*113T>G		downstream_gene	N/A

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

GnomAD2 exomes AF: 0.652 AC: 163641 AN: 251122 AF XY: 0.653

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 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

African (AFR) AF: 0.823 AC: 27552 AN: 33472

American (AMR) AF: 0.605 AC: 27055 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 19218 AN: 26086

East Asian (EAS) AF: 0.563 AC: 22349 AN: 39686

South Asian (SAS) AF: 0.705 AC: 60756 AN: 86220

European-Finnish (FIN) AF: 0.675 AC: 36065 AN: 53392

Middle Eastern (MID) AF: 0.778 AC: 4487 AN: 5766

European-Non Finnish (NFE) AF: 0.631 AC: 700662 AN: 1110920

Other (OTH) AF: 0.667 AC: 40276 AN: 60340

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

African (AFR) AF: 0.805 AC: 33420 AN: 41512

American (AMR) AF: 0.620 AC: 9476 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2561 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2827 AN: 5164

South Asian (SAS) AF: 0.697 AC: 3361 AN: 4820

European-Finnish (FIN) AF: 0.678 AC: 7156 AN: 10554

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42958 AN: 67972

Other (OTH) AF: 0.694 AC: 1465 AN: 2110

Alfa AF: 0.653 Hom.: 125595

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 v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.0052	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-2.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	5.0	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.13
ClinPred		0.00043	T
GERP RS		2.1
Varity_R		0.042
gMVP		0.013
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: rs3732782; hg19: chr3-113955164; COSMIC: COSV100351923; COSMIC: COSV100351923;