rs17381664

Positions:

• chr1-77582646-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015534.6(ZZZ3):​c.1645-520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 148,778 control chromosomes in the GnomAD database, including 7,839 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 0.29 (7839 hom., cov: 31)
• Consequence: ZZZ3 NM_015534.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

ZZZ3 (HGNC:24523): (zinc finger ZZ-type containing 3) Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in histone H4 acetylation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZZZ3	NM_015534.6	c.1645-520A>G		intron_variant		ENST00000370801.8	NP_056349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZZZ3	ENST00000370801.8	c.1645-520A>G		intron_variant		1	NM_015534.6	ENSP00000359837	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 42792 AN: 148716 Hom.: 7833 Cov.: 31

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00358

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.288 AC: 42803 AN: 148778 Hom.: 7839 Cov.: 31 AF XY: 0.288 AC XY: 20882 AN XY: 72472

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.00359

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.246

Alfa AF: 0.340 Hom.: 12025

Bravo AF: 0.279

Asia WGS AF: 0.0940 AC: 328 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs17381664; hg19: chr1-78048331; COSMIC: COSV66231819;