chr1-247300877-C-T

Variant names:

• chr1-247300877-C-T
• NM_032752.3:c.1406G>A

Variant summary

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

The NM_032752.3(ZNF496):​c.1406G>A​(p.Gly469Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF496 NM_032752.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.409
• Publications: 0 publications found

Genes affected

ZNF496 (HGNC:23713): (zinc finger protein 496) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein self-association. Predicted to be involved in positive regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032752.3. 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
	ZNF496	NM_032752.3	MANE Select	c.1406G>A	p.Gly469Glu	missense	Exon 10 of 10	NP_116141.1	Q96IT1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF496	ENST00000682384.1	MANE Select	c.1406G>A	p.Gly469Glu	missense	Exon 10 of 10	ENSP00000507236.1	Q96IT1-1
	ZNF496	ENST00000294753.8	TSL:1	c.1406G>A	p.Gly469Glu	missense	Exon 9 of 9	ENSP00000294753.4	Q96IT1-1
	ZNF496	ENST00000461277.2	TSL:1	c.1181G>A	p.Gly394Glu	missense	Exon 8 of 8	ENSP00000473324.1	A0A0C4DGR5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.41
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.15
Sift	Benign	0.037	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.10
MutPred		0.74		Loss of MoRF binding (P = 0.0471)
MVP		0.20
MPC		1.4
ClinPred		0.96	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.31
Mutation Taster		=56/44	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

hg19: chr1-247464179;