rs200300680

Variant names:

• chr19-12014924-C-G
• rs200300680
• NM_001308348.2:c.1934G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-12014924-C-G
• chr19-12014924-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001308348.2(ZNF433):​c.1934G>C​(p.Cys645Ser) 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 pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C645Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF433 NM_001308348.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF433	NM_001308348.2	c.1934G>C	p.Cys645Ser	missense_variant	Exon 4 of 4	ENST00000550507.7	NP_001295277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF433	ENST00000550507.7	c.1934G>C	p.Cys645Ser	missense_variant	Exon 4 of 4	2	NM_001308348.2	ENSP00000448099.2
ENSG00000286098	ENST00000652448.1	c.-94+13102C>G		intron_variant	Intron 2 of 4			ENSP00000498410.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250222 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135656

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.35	.;T
Eigen	Benign	0.069
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Pathogenic	3.9	.;H
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	.;D
Vest4		0.48
MutPred		0.74		.;Gain of disorder (P = 0.0501);
MVP		0.94
MPC		0.30
ClinPred		0.75	D
GERP RS		0.34
Varity_R		0.29
gMVP		0.040

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: rs200300680; hg19: chr19-12125739;