19-9301859-C-T

Variant names:

• chr19-9301859-C-T
• rs7252865
• NM_198535.3:c.175+519G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198535.3(ZNF699):​c.175+519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,226 control chromosomes in the GnomAD database, including 17,619 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 0.46 (17619 hom., cov: 31)
• Consequence: ZNF699 NM_198535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 8 publications found

Genes affected

ZNF699 (HGNC:24750): (zinc finger protein 699) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF699 Gene-Disease associations (from GenCC):

• DEGCAGS syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198535.3. 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
	ZNF699	NM_198535.3	MANE Select	c.175+519G>A		intron	N/A	NP_940937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF699	ENST00000591998.6	TSL:5 MANE Select	c.175+519G>A		intron	N/A	ENSP00000467723.1
	ZNF699	ENST00000308650.4	TSL:1	c.175+519G>A		intron	N/A	ENSP00000311596.3
	ZNF699	ENST00000952100.1		c.175+519G>A		intron	N/A	ENSP00000622159.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69649 AN: 151118 Hom.: 17621 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.461 AC: 69656 AN: 151226 Hom.: 17619 Cov.: 31 AF XY: 0.458 AC XY: 33855 AN XY: 73842

African (AFR) AF: 0.241 AC: 9928 AN: 41126

American (AMR) AF: 0.497 AC: 7581 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2228 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2273 AN: 5154

South Asian (SAS) AF: 0.573 AC: 2749 AN: 4800

European-Finnish (FIN) AF: 0.452 AC: 4661 AN: 10304

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38606 AN: 67834

Other (OTH) AF: 0.506 AC: 1061 AN: 2098

Alfa AF: 0.518 Hom.: 8067

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		-0.19
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: rs7252865; hg19: chr19-9412535;