Variant 1-77579636-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000370801.8(ZZZ3):c.1981-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,532,248 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 16 hom. )

Consequence

ZZZ3
ENST00000370801.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.03549

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.56

Variant links:

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]

ZZZ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-77579636-A-G is Benign according to our data. Variant chr1-77579636-A-G is described in ClinVar as [Benign]. Clinvar id is 715625.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 273 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZZZ3	NM_015534.6 linkuse as main transcript	c.1981-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370801.8	NP_056349.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZZZ3	ENST00000370801.8 linkuse as main transcript	c.1981-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015534.6	ENSP00000359837	P1	Q8IYH5-1
ZZZ3	ENST00000370798.5 linkuse as main transcript	c.499-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000359834		Q8IYH5-3
ZZZ3	ENST00000481346.5 linkuse as main transcript	n.545-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
ZZZ3	ENST00000476275.5 linkuse as main transcript	n.2864T>C	non_coding_transcript_exon_variant	5/10	2

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00203

AC:

411

AN:

202646

Hom.:

AF XY:

0.00243

AC XY:

270

AN XY:

111108

show subpopulations

Gnomad AFR exome

AF:

0.000541

Gnomad AMR exome

AF:

0.000504

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00302

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00327

AC:

4508

AN:

1379894

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

2270

AN XY:

687742

show subpopulations

Gnomad4 AFR exome

AF:

0.000620

Gnomad4 AMR exome

AF:

0.000726

Gnomad4 ASJ exome

AF:

0.0000819

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152354

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00170

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.035

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over