NM_001320371.4:c.1327G>A

Variant names:

• chr19-56384090-C-T
• NM_001320371.4:c.1327G>A

Variant summary

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

The NM_001320371.4(ZNF582):​c.1327G>A​(p.Val443Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF582 NM_001320371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.17
• Publications: 0 publications found

Genes affected

ZNF582 (HGNC:26421): (zinc finger protein 582) The protein encoded by this gene is a zing finger protein and putative transcription factor that is highly methylated in cervical cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ENSG00000285996 (HGNC:):

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=0.032918453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320371.4. 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
	ZNF582	NM_001320371.4	MANE Select	c.1327G>A	p.Val443Ile	missense	Exon 5 of 5	NP_001307300.2	Q96NG8
	ZNF582	NM_144690.3		c.1327G>A	p.Val443Ile	missense	Exon 5 of 5	NP_653291.1	Q96NG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF582	ENST00000586929.6	TSL:1 MANE Select	c.1327G>A	p.Val443Ile	missense	Exon 5 of 5	ENSP00000465619.1	Q96NG8
	ZNF582	ENST00000301310.8	TSL:1	c.1327G>A	p.Val443Ile	missense	Exon 5 of 5	ENSP00000301310.3	Q96NG8
	ZNF582	ENST00000932869.1		c.1327G>A	p.Val443Ile	missense	Exon 5 of 5	ENSP00000602928.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459480 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726026

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 85812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110990

Other (OTH) AF: 0.00 AC: 0 AN: 60284

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	0.083
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.82
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.13	N
PhyloP100		-4.2
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.019
Sift	Benign	0.039	D
Sift4G	Uncertain	0.025	D
Polyphen		0.0020	B
Vest4		0.049
MutPred		0.45		Loss of ubiquitination at K448 (P = 0.1062)
MVP		0.061
MPC		0.12
ClinPred		0.12	T
GERP RS		-9.1
Varity_R		0.037
gMVP		0.029
Mutation Taster		=97/3	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: chr19-56895459;