rs17381664

Variant names:

• chr1-77582646-T-C
• rs17381664
• NM_015534.6:c.1645-520A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015534.6. 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
	ZZZ3	NM_015534.6	MANE Select	c.1645-520A>G		intron	N/A	NP_056349.1	Q8IYH5-1
	ZZZ3	NM_001376146.1		c.1645-520A>G		intron	N/A	NP_001363075.1	Q8IYH5-1
	ZZZ3	NM_001376147.1		c.1645-520A>G		intron	N/A	NP_001363076.1	Q8IYH5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZZZ3	ENST00000370801.8	TSL:1 MANE Select	c.1645-520A>G		intron	N/A	ENSP00000359837.3	Q8IYH5-1
	ZZZ3	ENST00000370798.5	TSL:1	c.163-520A>G		intron	N/A	ENSP00000359834.1	Q8IYH5-3
	ZZZ3	ENST00000481346.5	TSL:1	n.212-520A>G		intron	N/A

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

African (AFR) AF: 0.0955 AC: 3871 AN: 40540

American (AMR) AF: 0.424 AC: 6327 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3456

East Asian (EAS) AF: 0.00359 AC: 18 AN: 5016

South Asian (SAS) AF: 0.250 AC: 1183 AN: 4740

European-Finnish (FIN) AF: 0.394 AC: 3713 AN: 9414

Middle Eastern (MID) AF: 0.189 AC: 53 AN: 280

European-Non Finnish (NFE) AF: 0.389 AC: 26224 AN: 67440

Other (OTH) AF: 0.246 AC: 507 AN: 2060

Alfa AF: 0.341 Hom.: 28781

Bravo AF: 0.279

Asia WGS AF: 0.0940 AC: 328 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.40
PhyloP100		-1.6
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: rs17381664; hg19: chr1-78048331; COSMIC: COSV66231819;