19-9298599-C-G

Variant names:

• chr19-9298599-C-G
• rs7254880
• NM_198535.3:c.176-609G>C

Variant summary

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

The NM_198535.3(ZNF699):​c.176-609G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,068 control chromosomes in the GnomAD database, including 3,116 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 0.16 (3116 hom., cov: 32)
• Consequence: ZNF699 NM_198535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 3 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 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.176-609G>C		intron	N/A	NP_940937.1	Q32M78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF699	ENST00000591998.6	TSL:5 MANE Select	c.176-609G>C		intron	N/A	ENSP00000467723.1	Q32M78
	ZNF699	ENST00000308650.4	TSL:1	c.176-609G>C		intron	N/A	ENSP00000311596.3	Q32M78
	ZNF699	ENST00000952100.1		c.176-1120G>C		intron	N/A	ENSP00000622159.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24193 AN: 151950 Hom.: 3107 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.159 AC: 24247 AN: 152068 Hom.: 3116 Cov.: 32 AF XY: 0.155 AC XY: 11536 AN XY: 74346

African (AFR) AF: 0.355 AC: 14709 AN: 41408

American (AMR) AF: 0.112 AC: 1705 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.0430 AC: 223 AN: 5188

South Asian (SAS) AF: 0.101 AC: 486 AN: 4824

European-Finnish (FIN) AF: 0.0423 AC: 448 AN: 10582

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5869 AN: 67994

Other (OTH) AF: 0.146 AC: 308 AN: 2114

Alfa AF: 0.128 Hom.: 262

Bravo AF: 0.175

Asia WGS AF: 0.110 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		0.066
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: rs7254880; hg19: chr19-9409275;