rs10410711

Variant names:

• chr19-36449796-A-G
• rs10410711
• NM_001145344.1:c.438T>C

Variant summary

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

The NM_001145344.1(ZNF566):​c.438T>C​(p.His146His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,614,094 control chromosomes in the GnomAD database, including 981 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 0.036 (138 hom., cov: 32)
  • Exomes 𝑓: 0.027 (843 hom.)
• Consequence: ZNF566 NM_001145344.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 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.438T>C	p.His146His	synonymous	Exon 5 of 5	NP_001138816.1
	ZNF566	NM_001145343.1		c.441T>C	p.His147His	synonymous	Exon 5 of 5	NP_001138815.1
	ZNF566	NM_001437584.1		c.441T>C	p.His147His	synonymous	Exon 5 of 5	NP_001424513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF566	ENST00000452939.7	TSL:2 MANE Select	c.438T>C	p.His146His	synonymous	Exon 5 of 5	ENSP00000411526.2
	ZNF566	ENST00000493391.6	TSL:1	c.126T>C	p.His42His	synonymous	Exon 3 of 3	ENSP00000465343.1
	ZNF566	ENST00000392170.7	TSL:5	c.441T>C	p.His147His	synonymous	Exon 5 of 5	ENSP00000376010.2

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5490 AN: 152134 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0329 AC: 8271 AN: 251396 AF XY: 0.0318

Gnomad AFR exome AF: 0.0596

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.0512

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0252

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0272 AC: 39756 AN: 1461842 Hom.: 843 Cov.: 31 AF XY: 0.0271 AC XY: 19685 AN XY: 727220

African (AFR) AF: 0.0641 AC: 2146 AN: 33478

American (AMR) AF: 0.0155 AC: 694 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 1432 AN: 26132

East Asian (EAS) AF: 0.138 AC: 5486 AN: 39684

South Asian (SAS) AF: 0.0235 AC: 2024 AN: 86256

European-Finnish (FIN) AF: 0.0241 AC: 1288 AN: 53418

Middle Eastern (MID) AF: 0.0312 AC: 180 AN: 5768

European-Non Finnish (NFE) AF: 0.0221 AC: 24548 AN: 1111988

Other (OTH) AF: 0.0324 AC: 1958 AN: 60394

GnomAD4 genome AF: 0.0362 AC: 5504 AN: 152252 Hom.: 138 Cov.: 32 AF XY: 0.0361 AC XY: 2685 AN XY: 74446

African (AFR) AF: 0.0602 AC: 2501 AN: 41540

American (AMR) AF: 0.0212 AC: 324 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.122 AC: 630 AN: 5176

South Asian (SAS) AF: 0.0242 AC: 117 AN: 4830

European-Finnish (FIN) AF: 0.0240 AC: 254 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1418 AN: 68020

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0272 Hom.: 160

Bravo AF: 0.0381

Asia WGS AF: 0.0760 AC: 262 AN: 3478

EpiCase AF: 0.0236

EpiControl AF: 0.0235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		0.0030
PromoterAI		0.0036	Neutral
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: rs10410711; hg19: chr19-36940698; COSMIC: COSV67574376; COSMIC: COSV67574376;