NM_001308348.2:c.1330G>C

Variant names:

• chr19-12015528-C-G
• rs775914267
• NM_001308348.2:c.1330G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308348.2(ZNF433):​c.1330G>C​(p.Glu444Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZNF433 NM_001308348.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

ZNF433 (HGNC:20811): (zinc finger protein 433) 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]

ENSG00000286098 (HGNC:):

ZNF433-AS1 (HGNC:53776): (ZNF433 and ZNF878 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18757656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308348.2. 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
	ZNF433	NM_001308348.2	MANE Select	c.1330G>C	p.Glu444Gln	missense	Exon 4 of 4	NP_001295277.1	F8VTV7
	ZNF433	NM_001080411.3		c.1339G>C	p.Glu447Gln	missense	Exon 4 of 4	NP_001073880.1	Q8N7K0-1
	ZNF433	NM_001308346.2		c.1336G>C	p.Glu446Gln	missense	Exon 5 of 5	NP_001295275.1	F8W0C9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF433	ENST00000550507.7	TSL:2 MANE Select	c.1330G>C	p.Glu444Gln	missense	Exon 4 of 4	ENSP00000448099.2	F8VTV7
	ZNF433	ENST00000478765.6	TSL:1	c.1372G>C	p.Glu458Gln	missense	Exon 3 of 3	ENSP00000447951.2	C9JQA6
	ZNF433	ENST00000419886.7	TSL:1	c.1234G>C	p.Glu412Gln	missense	Exon 5 of 5	ENSP00000393416.2	Q8N7K0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.035
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.070
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.32		Loss of ubiquitination at K448 (P = 0.0353)
MVP		0.30
MPC		0.26
ClinPred		0.97	D
GERP RS		1.2
Varity_R		0.21
gMVP		0.014
Mutation Taster		=96/4	polymorphism

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: rs775914267; hg19: chr19-12126343;