19-43847542-C-T

Position:

• chr19-43847542-C-T

Variant summary

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

The NM_181845.2(ZNF283):​c.941C>T​(p.Thr314Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,612,808 control chromosomes in the GnomAD database, including 580,382 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.85 (55774 hom., cov: 29)
  • Exomes 𝑓: 0.84 (524608 hom.)
• Consequence: ZNF283 NM_181845.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.9191325E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF283	NM_181845.2	c.941C>T	p.Thr314Ile	missense_variant	7/7	ENST00000618787.5	NP_862828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF283	ENST00000618787.5	c.941C>T	p.Thr314Ile	missense_variant	7/7	2	NM_181845.2	ENSP00000484852	A2
ZNF283	ENST00000324461.9	c.941C>T	p.Thr314Ile	missense_variant	4/4	1		ENSP00000327314	A2
ZNF283	ENST00000650832.1	c.833C>T	p.Thr278Ile	missense_variant	7/7			ENSP00000498705	P2
ZNF283	ENST00000588797.6	c.*541C>T		3_prime_UTR_variant	6/6	2		ENSP00000468708

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129076 AN: 151058 Hom.: 55722 Cov.: 29

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.842

GnomAD3 exomes AF: 0.806 AC: 201650 AN: 250176 Hom.: 82807 AF XY: 0.815 AC XY: 110538 AN XY: 135662

Gnomad AFR exome AF: 0.951

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.586

Gnomad SAS exome AF: 0.856

Gnomad FIN exome AF: 0.877

Gnomad NFE exome AF: 0.851

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.845 AC: 1234993 AN: 1461632 Hom.: 524608 Cov.: 75 AF XY: 0.846 AC XY: 615217 AN XY: 727120

Gnomad4 AFR exome AF: 0.951

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.803

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.856

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.838

GnomAD4 genome AF: 0.855 AC: 129184 AN: 151176 Hom.: 55774 Cov.: 29 AF XY: 0.852 AC XY: 62904 AN XY: 73872

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.841

Alfa AF: 0.857 Hom.: 23655

Bravo AF: 0.841

TwinsUK AF: 0.854 AC: 3166

ALSPAC AF: 0.857 AC: 3303

ESP6500AA AF: 0.947 AC: 4114

ESP6500EA AF: 0.858 AC: 7342

ExAC AF: 0.817 AC: 99053

Asia WGS AF: 0.772 AC: 2685 AN: 3478

EpiCase AF: 0.858

EpiControl AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.018	.;T;T
MetaRNN	Benign	5.9e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	.;.;D
REVEL	Benign	0.034
Sift	Benign	0.14	.;.;T
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.0	B;.;B
Vest4		0.098
MPC		0.25
ClinPred		0.022	T
GERP RS		2.0
Varity_R		0.14
gMVP		0.012

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: rs2195980; hg19: chr19-44351694; COSMIC: COSV61030739;