19-14705058-C-G

Variant names:

• chr19-14705058-C-G
• NM_032433.4:c.311C>G

Variant summary

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

The NM_032433.4(ZNF333):​c.311C>G​(p.Pro104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P104L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF333 NM_032433.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.921
• Publications: 0 publications found

Genes affected

ZNF333 (HGNC:15624): (zinc finger protein 333) 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]

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=0.144225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032433.4. 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
	ZNF333	NM_032433.4	MANE Select	c.311C>G	p.Pro104Arg	missense	Exon 6 of 12	NP_115809.1	Q96JL9-1
	ZNF333	NM_001352244.2		c.311C>G	p.Pro104Arg	missense	Exon 6 of 12	NP_001339173.1
	ZNF333	NM_001300912.2		c.311C>G	p.Pro104Arg	missense	Exon 6 of 12	NP_001287841.1	Q96JL9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF333	ENST00000292530.11	TSL:1 MANE Select	c.311C>G	p.Pro104Arg	missense	Exon 6 of 12	ENSP00000292530.5	Q96JL9-1
	ZNF333	ENST00000540689.6	TSL:1	c.311C>G	p.Pro104Arg	missense	Exon 6 of 12	ENSP00000438130.1	Q96JL9-3
	ZNF333	ENST00000597007.5	TSL:1	n.*304C>G		non_coding_transcript_exon	Exon 7 of 10	ENSP00000471574.1	M0R113

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.092
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.95
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.92
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.072
Sift	Benign	0.069	T
Sift4G	Uncertain	0.013	D
Polyphen		0.82	P
Vest4		0.35
MutPred		0.29		Gain of MoRF binding (P = 0.0041)
MVP		0.22
MPC		0.51
ClinPred		0.48	T
GERP RS		-3.9
Varity_R		0.055
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr19-14815870;