19-43850086-T-C

Variant names:

• chr19-43850086-T-C
• rs1549957
• NM_181845.2:c.*1445T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181845.2(ZNF283):​c.*1445T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,972 control chromosomes in the GnomAD database, including 12,883 homozygotes. 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: 𝑓 0.40 (12883 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ZNF283 NM_181845.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• Publications: 4 publications found

Genes affected

ZNF283 (HGNC:13077): (zinc finger protein 283) 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 (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF283	NM_181845.2	c.*1445T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000618787.5	NP_862828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF283	ENST00000618787.5	c.*1445T>C		3_prime_UTR_variant	Exon 7 of 7	2	NM_181845.2	ENSP00000484852.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61498 AN: 151852 Hom.: 12872 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.405 AC: 61534 AN: 151970 Hom.: 12883 Cov.: 32 AF XY: 0.405 AC XY: 30043 AN XY: 74244

African (AFR) AF: 0.450 AC: 18634 AN: 41422

American (AMR) AF: 0.257 AC: 3931 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1446 AN: 3460

East Asian (EAS) AF: 0.217 AC: 1126 AN: 5182

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4814

European-Finnish (FIN) AF: 0.475 AC: 5010 AN: 10550

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27611 AN: 67940

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.262 Hom.: 643

Bravo AF: 0.385

Asia WGS AF: 0.365 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		-0.92

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: rs1549957; hg19: chr19-44354238;