19-56384018-C-T

Variant names:

• chr19-56384018-C-T
• rs141898302
• NM_001320371.4:c.1399G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320371.4(ZNF582):​c.1399G>A​(p.Val467Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,548 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: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: ZNF582 NM_001320371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.65
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023524582).

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.1399G>A	p.Val467Ile	missense	Exon 5 of 5	NP_001307300.2	Q96NG8
	ZNF582	NM_144690.3		c.1399G>A	p.Val467Ile	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.1399G>A	p.Val467Ile	missense	Exon 5 of 5	ENSP00000465619.1	Q96NG8
	ZNF582	ENST00000301310.8	TSL:1	c.1399G>A	p.Val467Ile	missense	Exon 5 of 5	ENSP00000301310.3	Q96NG8
	ZNF582	ENST00000932869.1		c.1399G>A	p.Val467Ile	missense	Exon 5 of 5	ENSP00000602928.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250630 AF XY: 0.000111

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000732 AC: 107 AN: 1461406 Hom.: 0 Cov.: 31 AF XY: 0.0000784 AC XY: 57 AN XY: 726980

African (AFR) AF: 0.0000897 AC: 3 AN: 33458

American (AMR) AF: 0.0000224 AC: 1 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.000337 AC: 29 AN: 86122

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53374

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111878

Other (OTH) AF: 0.0000662 AC: 4 AN: 60378

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74336

African (AFR) AF: 0.000121 AC: 5 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.065
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0070
DANN	Benign	0.46
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.0087	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-5.7
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.011
Sift	Benign	0.69	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.025
MVP		0.061
MPC		0.10
ClinPred		0.018	T
GERP RS		-8.2
Varity_R		0.024
gMVP		0.021
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: rs141898302; hg19: chr19-56895387; COSMIC: COSV100018753; COSMIC: COSV100018753;