rs10235235

Variant names:

• chr7-99478208-T-C
• rs10235235
• NM_213603.3:c.25-1453T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213603.3. 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
	ZNF789	NM_213603.3	MANE Select	c.25-1453T>C		intron	N/A	NP_998768.2	Q5FWF6-1
	ZNF789	NM_001350999.2		c.-27-1453T>C		intron	N/A	NP_001337928.1
	ZNF789	NM_001351000.2		c.25-1453T>C		intron	N/A	NP_001337929.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF789	ENST00000331410.10	TSL:1 MANE Select	c.25-1453T>C		intron	N/A	ENSP00000331927.5	Q5FWF6-1
	ZNF789	ENST00000448667.5	TSL:1	c.-80-66T>C		intron	N/A	ENSP00000405206.1	C9J487
	ZNF789	ENST00000483089.5	TSL:1	c.-80-66T>C		intron	N/A	ENSP00000417227.1	C9J3R7

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

African (AFR) AF: 0.236 AC: 5108 AN: 21620

American (AMR) AF: 0.0859 AC: 2223 AN: 25878

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 1101 AN: 13836

East Asian (EAS) AF: 0.00194 AC: 23 AN: 11834

South Asian (SAS) AF: 0.0681 AC: 4862 AN: 71414

European-Finnish (FIN) AF: 0.149 AC: 1825 AN: 12284

Middle Eastern (MID) AF: 0.0888 AC: 254 AN: 2860

European-Non Finnish (NFE) AF: 0.0861 AC: 69529 AN: 807232

Other (OTH) AF: 0.0864 AC: 3148 AN: 36428

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

African (AFR) AF: 0.225 AC: 9322 AN: 41466

American (AMR) AF: 0.0985 AC: 1506 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5178

South Asian (SAS) AF: 0.0666 AC: 321 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5653 AN: 67990

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.0932 Hom.: 825

Bravo AF: 0.125

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10235235; hg19: chr7-99075831;