1-247301264-G-T

Variant names:

• chr1-247301264-G-T
• NM_032752.3:c.1019C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032752.3(ZNF496):​c.1019C>A​(p.Pro340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P340L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ZNF496 NM_032752.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057834566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF496	NM_032752.3	c.1019C>A	p.Pro340Gln	missense_variant	Exon 10 of 10	ENST00000682384.1	NP_116141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF496	ENST00000682384.1	c.1019C>A	p.Pro340Gln	missense_variant	Exon 10 of 10		NM_032752.3	ENSP00000507236.1
ZNF496	ENST00000294753.8	c.1019C>A	p.Pro340Gln	missense_variant	Exon 9 of 9	1		ENSP00000294753.4
ZNF496	ENST00000461277.2	c.794C>A	p.Pro265Gln	missense_variant	Exon 8 of 8	1		ENSP00000473324.1
ZNF496	ENST00000462139.1	n.5391C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1360392 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 666092

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: 0.0000223

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.4
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.060
Sift	Benign	0.29	T;.
Sift4G	Benign	0.45	T;T
Polyphen		0.80	P;.
Vest4		0.11
MutPred		0.15		Loss of glycosylation at S342 (P = 0.0858);.;
MVP		0.35
MPC		0.44
ClinPred		0.062	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.31

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: chr1-247464566;