NM_001145344.1:c.10-716C>A

Variant names:

• chr19-36474174-G-T
• rs10421862
• NM_001145344.1:c.10-716C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145344.1(ZNF566):​c.10-716C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,192 control chromosomes in the GnomAD database, including 851 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (851 hom., cov: 32)
• Consequence: ZNF566 NM_001145344.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 3 publications found

Genes affected

ZNF566 (HGNC:25919): (zinc finger protein 566) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF566	NM_001145344.1	MANE Select	c.10-716C>A		intron	N/A	NP_001138816.1
	ZNF566	NM_001145343.1		c.10-716C>A		intron	N/A	NP_001138815.1
	ZNF566	NM_001437584.1		c.10-716C>A		intron	N/A	NP_001424513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF566	ENST00000452939.7	TSL:2 MANE Select	c.10-716C>A		intron	N/A	ENSP00000411526.2
	ZNF566	ENST00000493391.6	TSL:1	c.-81+2375C>A		intron	N/A	ENSP00000465343.1
	ZNF566	ENST00000392170.7	TSL:5	c.10-716C>A		intron	N/A	ENSP00000376010.2

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15094 AN: 152074 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0918

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0993 AC: 15119 AN: 152192 Hom.: 851 Cov.: 32 AF XY: 0.0981 AC XY: 7298 AN XY: 74398

African (AFR) AF: 0.158 AC: 6569 AN: 41532

American (AMR) AF: 0.0630 AC: 962 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.0854 AC: 442 AN: 5176

South Asian (SAS) AF: 0.0430 AC: 207 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10590

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5334 AN: 68014

Other (OTH) AF: 0.0913 AC: 193 AN: 2114

Alfa AF: 0.0821 Hom.: 927

Bravo AF: 0.101

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		0.17
Mutation Taster		=100/0	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: rs10421862; hg19: chr19-36965076;