chr19-43847233-A-C

Variant names:

• chr19-43847233-A-C
• rs1971438312
• NM_181845.2:c.632A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181845.2(ZNF283):​c.632A>C​(p.Glu211Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF283 NM_181845.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18884468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181845.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF283	NM_181845.2	MANE Select	c.632A>C	p.Glu211Ala	missense	Exon 7 of 7	NP_862828.1	Q8N7M2
	ZNF283	NM_001297752.2		c.215A>C	p.Glu72Ala	missense	Exon 6 of 6	NP_001284681.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF283	ENST00000618787.5	TSL:2 MANE Select	c.632A>C	p.Glu211Ala	missense	Exon 7 of 7	ENSP00000484852.1	Q8N7M2
	ZNF283	ENST00000324461.9	TSL:1	c.632A>C	p.Glu211Ala	missense	Exon 4 of 4	ENSP00000327314.7	Q8N7M2
	ZNF283	ENST00000650832.1		c.524A>C	p.Glu175Ala	missense	Exon 7 of 7	ENSP00000498705.1	A0A494C0U8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.4
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.045
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.014	D
Polyphen		0.35	B
Vest4		0.20
MutPred		0.47		Loss of solvent accessibility (P = 0.0224)
MVP		0.47
MPC		0.38
ClinPred		0.31	T
GERP RS		3.5
Varity_R		0.20
gMVP		0.039
Mutation Taster		=99/1	polymorphism

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: rs1971438312; hg19: chr19-44351385;