rs10235235

Positions:

• chr7-99478208-T-C

Variant summary

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

The NM_213603.3(ZNF789):​c.25-1453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 1,155,498 control chromosomes in the GnomAD database, including 5,944 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 0.13 (1570 hom., cov: 32)
  • Exomes 𝑓: 0.088 (4374 hom.)
• Consequence: ZNF789 NM_213603.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

Genes affected

ZNF789 (HGNC:27801): (zinc finger protein 789) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF394 (HGNC:18832): (zinc finger protein 394) The protein encoded by this gene is a zinc finger protein that inhibits the transcription of mitogen-activated protein kinase signaling pathways. The encoded protein may be involved in cardiac function. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF789	NM_213603.3	c.25-1453T>C		intron_variant		ENST00000331410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF789	ENST00000331410.10	c.25-1453T>C		intron_variant		1	NM_213603.3	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19071 AN: 151994 Hom.: 1561 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.0878 AC: 88073 AN: 1003386 Hom.: 4374 AF XY: 0.0872 AC XY: 42942 AN XY: 492472

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.0859

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.00194

Gnomad4 SAS exome AF: 0.0681

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.0861

Gnomad4 OTH exome AF: 0.0864

GnomAD4 genome AF: 0.126 AC: 19109 AN: 152112 Hom.: 1570 Cov.: 32 AF XY: 0.128 AC XY: 9493 AN XY: 74376

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0666

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0927 Hom.: 577

Bravo AF: 0.125

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10235235; hg19: chr7-99075831;