chr19-56414035-A-G

Variant names:

• chr19-56414035-A-G
• NM_152478.3:c.86A>G

Variant summary

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

The NM_152478.3(ZNF583):​c.86A>G​(p.Asn29Ser) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF583 NM_152478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.468
• Publications: 0 publications found

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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=0.06742531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152478.3. 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
	ZNF583	NM_152478.3	MANE Select	c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	NP_689691.2	Q96ND8
	ZNF583	NM_001159860.2		c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	NP_001153332.1	Q96ND8
	ZNF583	NM_001159861.2		c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	NP_001153333.1	Q96ND8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF583	ENST00000333201.13	TSL:2 MANE Select	c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	ENSP00000388502.2	Q96ND8
	ZNF583	ENST00000890730.1		c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	ENSP00000560789.1
	ZNF583	ENST00000969490.1		c.86A>G	p.Asn29Ser	missense	Exon 3 of 5	ENSP00000639549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.82
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.43	N
PhyloP100		-0.47
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.040
Sift	Benign	0.19	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.52		Gain of MoRF binding (P = 0.1079)
MVP		0.27
MPC		0.41
ClinPred		0.029	T
GERP RS		-1.5
Varity_R		0.034
gMVP		0.14
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

hg19: chr19-56925404;