rs12460279

Variant names:

• chr19-9300678-A-G
• rs12460279
• NM_198535.3:c.175+1700T>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.175+1700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,076 control chromosomes in the GnomAD database, including 17,628 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 (17628 hom., cov: 32)
• Consequence: ZNF699 NM_198535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 9 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=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF699	NM_198535.3	c.175+1700T>C		intron_variant	Intron 3 of 5	ENST00000591998.6	NP_940937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF699	ENST00000591998.6	c.175+1700T>C		intron_variant	Intron 3 of 5	5	NM_198535.3	ENSP00000467723.1
ZNF699	ENST00000308650.4	c.175+1700T>C		intron_variant	Intron 2 of 4	1		ENSP00000311596.3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69735 AN: 151958 Hom.: 17630 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.459 AC: 69743 AN: 152076 Hom.: 17628 Cov.: 32 AF XY: 0.456 AC XY: 33920 AN XY: 74316

African (AFR) AF: 0.240 AC: 9956 AN: 41512

American (AMR) AF: 0.496 AC: 7578 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2263 AN: 5148

South Asian (SAS) AF: 0.571 AC: 2751 AN: 4820

European-Finnish (FIN) AF: 0.446 AC: 4710 AN: 10572

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

European-Non Finnish (NFE) AF: 0.568 AC: 38634 AN: 67980

Other (OTH) AF: 0.501 AC: 1056 AN: 2108

Alfa AF: 0.487 Hom.: 2534

Bravo AF: 0.452

Asia WGS AF: 0.487 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		1.3
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: rs12460279; hg19: chr19-9411354;