19-57211833-C-G

Position:

• chr19-57211833-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003417.5(ZNF264):​c.736C>G​(p.Leu246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF264 NM_003417.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

ZNF264 (HGNC:13057): (zinc finger protein 264) This gene encodes a zinc finger protein and belongs to the krueppel C2H2-type zinc-finger protein family. Zinc finger proteins are often localized in the nucleus, bind nucleic acids, and regulate transcription. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF264	NM_003417.5	c.736C>G	p.Leu246Val	missense_variant	4/4	ENST00000263095.10	NP_003408.1
ZNF264	XM_047439724.1	c.736C>G	p.Leu246Val	missense_variant	5/5		XP_047295680.1
ZNF264	XM_011527522.3	c.640C>G	p.Leu214Val	missense_variant	3/3		XP_011525824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF264	ENST00000263095.10	c.736C>G	p.Leu246Val	missense_variant	4/4	2	NM_003417.5	ENSP00000263095.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727244

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: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.736C>G (p.L246V) alteration is located in exon 4 (coding exon 4) of the ZNF264 gene. This alteration results from a C to G substitution at nucleotide position 736, causing the leucine (L) at amino acid position 246 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	2.9	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.16
Sift	Benign	0.071	T;T
Sift4G	Uncertain	0.045	D;D
Polyphen		0.98	D;D
Vest4		0.35
MutPred		0.74		Gain of methylation at K242 (P = 0.0635);Gain of methylation at K242 (P = 0.0635);
MVP		0.32
MPC		0.36
ClinPred		0.73	D
GERP RS		2.4
Varity_R		0.13
gMVP		0.048

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: rs769785751; hg19: chr19-57723201;