rs769569044

Variant names:

• chr19-43847026-A-C
• rs769569044
• NM_181845.2:c.425A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-43847026-A-C
• chr19-43847026-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181845.2(ZNF283):​c.425A>C​(p.Asp142Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D142G) has been classified 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: 0.308
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061387718).

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.425A>C	p.Asp142Ala	missense	Exon 7 of 7	NP_862828.1	Q8N7M2
	ZNF283	NM_001297752.2		c.8A>C	p.Asp3Ala	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.425A>C	p.Asp142Ala	missense	Exon 7 of 7	ENSP00000484852.1	Q8N7M2
	ZNF283	ENST00000324461.9	TSL:1	c.425A>C	p.Asp142Ala	missense	Exon 4 of 4	ENSP00000327314.7	Q8N7M2
	ZNF283	ENST00000650832.1		c.317A>C	p.Asp106Ala	missense	Exon 7 of 7	ENSP00000498705.1	A0A494C0U8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

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	0.097
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.095	N
PhyloP100		0.31
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.024
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.28		Loss of ubiquitination at K145 (P = 0.0412)
MVP		0.21
MPC		0.30
ClinPred		0.051	T
GERP RS		2.6
Varity_R		0.10
gMVP		0.055
Mutation Taster		=95/5	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: rs769569044; hg19: chr19-44351178;