NM_144684.4:c.333C>T

Variant names:

• chr19-52321583-C-T
• rs377131707
• NM_144684.4:c.333C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144684.4(ZNF480):​c.333C>T​(p.Ser111Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZNF480 NM_144684.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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]

ENSG00000269535 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06638488).
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF480	NM_144684.4	c.333C>T	p.Ser111Ser	synonymous_variant	Exon 5 of 5	ENST00000595962.6	NP_653285.2
ZNF480	NM_001297624.2	c.204C>T	p.Ser68Ser	synonymous_variant	Exon 4 of 4		NP_001284553.1
ZNF480	NM_001297625.2	c.102C>T	p.Ser34Ser	synonymous_variant	Exon 4 of 4		NP_001284554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF480	ENST00000595962.6	c.333C>T	p.Ser111Ser	synonymous_variant	Exon 5 of 5	1	NM_144684.4	ENSP00000471754.1
ZNF480	ENST00000468240.6	n.333C>T		non_coding_transcript_exon_variant	Exon 5 of 6	2		ENSP00000417424.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424238 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 704362

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.5
DANN	Benign	0.44
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.92	T
PROVEAN	Benign	0.33	.;N
REVEL	Benign	0.013
Sift4G	Benign	0.11	T;.
Vest4		0.13
MutPred		0.30		.;Loss of disorder (P = 0.0375);
MVP		0.11
ClinPred		0.021	T
GERP RS		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs377131707; hg19: chr19-52824836; COSMIC: COSV99078283;