chr19-43847542-C-T

Variant names:

• chr19-43847542-C-T
• rs2195980
• NM_181845.2:c.941C>T

Variant summary

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

The ENST00000618787.5(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. 13/21 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 0.85 (55774 hom., cov: 29)
  • Exomes 𝑓: 0.84 (524608 hom.)
• Consequence: ZNF283 ENST00000618787.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 28 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 (MetaRNN=5.9191325E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000618787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF283	NM_181845.2	MANE Select	c.941C>T	p.Thr314Ile	missense	Exon 7 of 7	NP_862828.1
	ZNF283	NM_001297752.2		c.524C>T	p.Thr175Ile	missense	Exon 6 of 6	NP_001284681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF283	ENST00000618787.5	TSL:2 MANE Select	c.941C>T	p.Thr314Ile	missense	Exon 7 of 7	ENSP00000484852.1
	ZNF283	ENST00000324461.9	TSL:1	c.941C>T	p.Thr314Ile	missense	Exon 4 of 4	ENSP00000327314.7
	ZNF283	ENST00000650832.1		c.833C>T	p.Thr278Ile	missense	Exon 7 of 7	ENSP00000498705.1

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

GnomAD2 exomes AF: 0.806 AC: 201650 AN: 250176 AF XY: 0.815

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 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

African (AFR) AF: 0.951 AC: 31852 AN: 33478

American (AMR) AF: 0.634 AC: 28331 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 20985 AN: 26130

East Asian (EAS) AF: 0.608 AC: 24122 AN: 39690

South Asian (SAS) AF: 0.856 AC: 73800 AN: 86230

European-Finnish (FIN) AF: 0.873 AC: 46642 AN: 53412

Middle Eastern (MID) AF: 0.842 AC: 4855 AN: 5768

European-Non Finnish (NFE) AF: 0.858 AC: 953798 AN: 1111834

Other (OTH) AF: 0.838 AC: 50608 AN: 60390

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

African (AFR) AF: 0.943 AC: 38818 AN: 41164

American (AMR) AF: 0.705 AC: 10718 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2780 AN: 3460

East Asian (EAS) AF: 0.593 AC: 3005 AN: 5068

South Asian (SAS) AF: 0.854 AC: 4087 AN: 4786

European-Finnish (FIN) AF: 0.884 AC: 9279 AN: 10502

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57749 AN: 67688

Other (OTH) AF: 0.841 AC: 1767 AN: 2102

Alfa AF: 0.858 Hom.: 24010

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 v4.9

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
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.018	T
MetaRNN	Benign	5.9e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.55
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.034
Sift	Benign	0.14	T
Sift4G	Uncertain	0.034	D
Polyphen		0.0	B
Vest4		0.098
MPC		0.25
ClinPred		0.022	T
GERP RS		2.0
Varity_R		0.14
gMVP		0.012
Mutation Taster		=99/1	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: rs2195980; hg19: chr19-44351694; COSMIC: COSV61030739;