rs3217319

Variant names:

• chr19-52300416-CTG-C
• rs3217319
• NM_144684.4:c.9_10delTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144684.4(ZNF480):​c.9_10delTG​(p.Cys3fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,612,698 control chromosomes in the GnomAD database, including 415,545 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31645 hom., cov: 0)
  • Exomes 𝑓: 0.72 (383900 hom.)
• Consequence: ZNF480 NM_144684.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310
• Publications: 21 publications found

Genes affected

ZNF480 (HGNC:23305): (zinc finger protein 480) 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-52300416-CTG-C is Benign according to our data. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-52300416-CTG-C is described in CliVar as Benign. Clinvar id is 403625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF480	NM_144684.4	c.9_10delTG	p.Cys3fs	frameshift_variant	Exon 2 of 5	ENST00000595962.6	NP_653285.2
ZNF480	NM_001297624.2	c.9_10delTG	p.Cys3fs	frameshift_variant	Exon 2 of 4		NP_001284553.1
ZNF480	NM_001297625.2	c.-96_-95delTG		5_prime_UTR_variant	Exon 2 of 4		NP_001284554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF480	ENST00000595962.6	c.9_10delTG	p.Cys3fs	frameshift_variant	Exon 2 of 5	1	NM_144684.4	ENSP00000471754.1
ZNF480	ENST00000468240.6	n.9_10delTG		non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000417424.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95257 AN: 151508 Hom.: 31650 Cov.: 0

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.642

GnomAD2 exomes AF: 0.691 AC: 173530 AN: 251220 AF XY: 0.701

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.702

GnomAD4 exome AF: 0.722 AC: 1054817 AN: 1461072 Hom.: 383900 AF XY: 0.722 AC XY: 525143 AN XY: 726888

African (AFR) AF: 0.374 AC: 12536 AN: 33476

American (AMR) AF: 0.664 AC: 29707 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 16580 AN: 26128

East Asian (EAS) AF: 0.664 AC: 26378 AN: 39700

South Asian (SAS) AF: 0.729 AC: 62871 AN: 86246

European-Finnish (FIN) AF: 0.768 AC: 40865 AN: 53186

Middle Eastern (MID) AF: 0.619 AC: 3570 AN: 5766

European-Non Finnish (NFE) AF: 0.738 AC: 820337 AN: 1111482

Other (OTH) AF: 0.695 AC: 41973 AN: 60370

GnomAD4 genome AF: 0.628 AC: 95265 AN: 151626 Hom.: 31645 Cov.: 0 AF XY: 0.634 AC XY: 46961 AN XY: 74060

African (AFR) AF: 0.386 AC: 15934 AN: 41282

American (AMR) AF: 0.671 AC: 10218 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3234 AN: 5142

South Asian (SAS) AF: 0.743 AC: 3578 AN: 4818

European-Finnish (FIN) AF: 0.784 AC: 8209 AN: 10476

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49797 AN: 67902

Other (OTH) AF: 0.640 AC: 1345 AN: 2100

Alfa AF: 0.675 Hom.: 6504

Bravo AF: 0.609

Asia WGS AF: 0.631 AC: 2193 AN: 3478

EpiCase AF: 0.722

EpiControl AF: 0.729

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 7679/12518=61.35% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.031
Mutation Taster		=152/48	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: rs3217319; hg19: chr19-52803669; COSMIC: COSV57994418; COSMIC: COSV57994418;