19-12391197-C-T

Position:

• chr19-12391197-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080821.3(ZNF799):​c.1201G>A​(p.Ala401Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF799 NM_001080821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81

Genes affected

ZNF799 (HGNC:28071): (zinc finger protein 799) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF799 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05434692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3	c.1201G>A	p.Ala401Thr	missense_variant	4/4	ENST00000430385.3	NP_001074290.1
ZNF799	NM_001322497.2	c.1105G>A	p.Ala369Thr	missense_variant	4/4		NP_001309426.1
ZNF799	NM_001322498.2	c.1105G>A	p.Ala369Thr	missense_variant	5/5		NP_001309427.1
ZNF799	XM_047439649.1	c.1201G>A	p.Ala401Thr	missense_variant	4/4		XP_047295605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF799	ENST00000430385.3	c.1201G>A	p.Ala401Thr	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2
ZNF799	ENST00000460935.1	n.2895G>A		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5	c.1105G>A	p.Ala369Thr	missense_variant	4/4	2		ENSP00000415278.1
ENSG00000268744	ENST00000435033.1	n.208-7510G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461866 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.1201G>A (p.A401T) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a G to A substitution at nucleotide position 1201, causing the alanine (A) at amino acid position 401 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.75
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.052
Sift	Benign	0.16	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.023	.;B
Vest4		0.19
MutPred		0.53		.;Gain of disorder (P = 0.0904);
MVP		0.21
MPC		0.15
ClinPred		0.075	T
GERP RS		1.3
Varity_R		0.061
gMVP		0.0048

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: rs866933924; hg19: chr19-12502011;