chr19-56384127-C-T

Variant names:

• chr19-56384127-C-T
• rs12978696
• NM_001320371.4:c.1290G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001320371.4(ZNF582):​c.1290G>A​(p.Lys430Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,336 control chromosomes in the GnomAD database, including 15,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1314 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13943 hom.)
• Consequence: ZNF582 NM_001320371.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.519
• Publications: 10 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-56384127-C-T is Benign according to our data. Variant chr19-56384127-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058896.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

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.1290G>A	p.Lys430Lys	synonymous	Exon 5 of 5	NP_001307300.2	Q96NG8
	ZNF582	NM_144690.3		c.1290G>A	p.Lys430Lys	synonymous	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.1290G>A	p.Lys430Lys	synonymous	Exon 5 of 5	ENSP00000465619.1	Q96NG8
	ZNF582	ENST00000301310.8	TSL:1	c.1290G>A	p.Lys430Lys	synonymous	Exon 5 of 5	ENSP00000301310.3	Q96NG8
	ZNF582	ENST00000932869.1		c.1290G>A	p.Lys430Lys	synonymous	Exon 5 of 5	ENSP00000602928.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19264 AN: 152032 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.152 AC: 37867 AN: 249788 AF XY: 0.151

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.308

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.133 AC: 194605 AN: 1460186 Hom.: 13943 Cov.: 33 AF XY: 0.135 AC XY: 97701 AN XY: 726372

African (AFR) AF: 0.0981 AC: 3280 AN: 33420

American (AMR) AF: 0.157 AC: 6995 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4032 AN: 25978

East Asian (EAS) AF: 0.301 AC: 11936 AN: 39670

South Asian (SAS) AF: 0.161 AC: 13864 AN: 85972

European-Finnish (FIN) AF: 0.152 AC: 8105 AN: 53282

Middle Eastern (MID) AF: 0.148 AC: 849 AN: 5748

European-Non Finnish (NFE) AF: 0.123 AC: 137002 AN: 1111278

Other (OTH) AF: 0.142 AC: 8542 AN: 60314

GnomAD4 genome AF: 0.127 AC: 19299 AN: 152150 Hom.: 1314 Cov.: 32 AF XY: 0.128 AC XY: 9546 AN XY: 74374

African (AFR) AF: 0.101 AC: 4185 AN: 41524

American (AMR) AF: 0.117 AC: 1784 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1585 AN: 5170

South Asian (SAS) AF: 0.156 AC: 754 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1553 AN: 10578

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8521 AN: 67984

Other (OTH) AF: 0.129 AC: 271 AN: 2106

Alfa AF: 0.128 Hom.: 996

Bravo AF: 0.125

Asia WGS AF: 0.219 AC: 761 AN: 3478

EpiCase AF: 0.127

EpiControl AF: 0.131

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZNF582-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		-0.52
Mutation Taster		=99/1	polymorphism (auto)

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: rs12978696; hg19: chr19-56895496; COSMIC: COSV56732320; COSMIC: COSV56732320;