19-11722627-G-A

Variant names:

• chr19-11722627-G-A
• NM_001080493.4:c.907C>T

Variant summary

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

The NM_001080493.4(ZNF823):​c.907C>T​(p.Pro303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF823 NM_001080493.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08

Genes affected

ZNF823 (HGNC:30936): (zinc finger protein 823) 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]

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 rank	MANE	Protein	UniProt
ZNF823	NM_001080493.4	c.907C>T	p.Pro303Ser	missense_variant	Exon 4 of 4	ENST00000341191.11	NP_001073962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF823	ENST00000341191.11	c.907C>T	p.Pro303Ser	missense_variant	Exon 4 of 4	1	NM_001080493.4	ENSP00000340683.5
ZNF823	ENST00000431998.1	c.775C>T	p.Pro259Ser	missense_variant	Exon 3 of 3	1		ENSP00000410654.1
ZNF823	ENST00000586121.1	c.*84C>T		downstream_gene_variant		3		ENSP00000466840.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.907C>T (p.P303S) alteration is located in exon 4 (coding exon 4) of the ZNF823 gene. This alteration results from a C to T substitution at nucleotide position 907, causing the proline (P) at amino acid position 303 to be replaced by a serine (S). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Benign	0.23
Sift	Benign	0.045	D;D
Sift4G	Uncertain	0.030	D;.
Polyphen		1.0	D;.
Vest4		0.17
MutPred		0.58		Gain of ubiquitination at K307 (P = 0.1115);.;
MVP		0.58
MPC		1.3
ClinPred		0.95	D
GERP RS		-0.62
Varity_R		0.21
gMVP		0.011

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: chr19-11833442;