1-77623714-T-C

Variant names:

• chr1-77623714-T-C
• rs1389790
• NM_015534.6:c.1505+8136A>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.1505+8136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,056 control chromosomes in the GnomAD database, including 27,766 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 0.58 (27766 hom., cov: 31)
• Consequence: ZZZ3 NM_015534.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZZZ3	NM_015534.6	MANE Select	c.1505+8136A>G		intron	N/A	NP_056349.1
	ZZZ3	NM_001376146.1		c.1505+8136A>G		intron	N/A	NP_001363075.1
	ZZZ3	NM_001376147.1		c.1505+8136A>G		intron	N/A	NP_001363076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZZZ3	ENST00000370801.8	TSL:1 MANE Select	c.1505+8136A>G		intron	N/A	ENSP00000359837.3
	ZZZ3	ENST00000370798.5	TSL:1	c.23+15735A>G		intron	N/A	ENSP00000359834.1
	ZZZ3	ENST00000481346.5	TSL:1	n.72+8136A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88001 AN: 151938 Hom.: 27760 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.579 AC: 88023 AN: 152056 Hom.: 27766 Cov.: 31 AF XY: 0.576 AC XY: 42794 AN XY: 74322

African (AFR) AF: 0.317 AC: 13158 AN: 41488

American (AMR) AF: 0.696 AC: 10628 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3466

East Asian (EAS) AF: 0.627 AC: 3235 AN: 5162

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4818

European-Finnish (FIN) AF: 0.653 AC: 6900 AN: 10572

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48113 AN: 67968

Other (OTH) AF: 0.549 AC: 1153 AN: 2102

Alfa AF: 0.665 Hom.: 19242

Bravo AF: 0.574

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1389790; hg19: chr1-78089399;