19-12391238-T-G

Position:

• chr19-12391238-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080821.3(ZNF799):​c.1160A>C​(p.His387Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF799 NM_001080821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF799	NM_001080821.3	c.1160A>C	p.His387Pro	missense_variant	4/4	ENST00000430385.3	NP_001074290.1
ZNF799	NM_001322497.2	c.1064A>C	p.His355Pro	missense_variant	4/4		NP_001309426.1
ZNF799	NM_001322498.2	c.1064A>C	p.His355Pro	missense_variant	5/5		NP_001309427.1
ZNF799	XM_047439649.1	c.1160A>C	p.His387Pro	missense_variant	4/4		XP_047295605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF799	ENST00000430385.3	c.1160A>C	p.His387Pro	missense_variant	4/4	2	NM_001080821.3	ENSP00000411084.2
ZNF799	ENST00000460935.1	n.2854A>C		non_coding_transcript_exon_variant	3/3	1
ZNF799	ENST00000419318.5	c.1064A>C	p.His355Pro	missense_variant	4/4	2		ENSP00000415278.1
ENSG00000268744	ENST00000435033.1	n.208-7551A>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 28, 2022

The c.1160A>C (p.H387P) alteration is located in exon 4 (coding exon 4) of the ZNF799 gene. This alteration results from a A to C substitution at nucleotide position 1160, causing the histidine (H) at amino acid position 387 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.30	.;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.5	.;H
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-8.9	D;D
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.28
MutPred		0.74		.;Gain of glycosylation at T388 (P = 0.0609);
MVP		0.90
MPC		0.59
ClinPred		1.0	D
GERP RS		1.3
Varity_R		0.62
gMVP		0.064

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-12502052;