chr2-27617543-A-G

Position:

• chr2-27617543-A-G

Variant summary

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

The NM_032434.4(ZNF512):​c.1367A>G​(p.Lys456Arg) variant causes a missense change involving the alteration of a 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF512 NM_032434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

Genes affected

ZNF512 (HGNC:29380): (zinc finger protein 512) This gene encodes a protein containing four putative zinc finger motifs. Zinc finger motifs may bind to proteins or nucleic acids. Zinc finger-containing proteins are involved in a variety of processes, including regulation of transcription. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Sep 2012]

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
ZNF512	NM_032434.4	c.1367A>G	p.Lys456Arg	missense_variant	13/14	ENST00000355467.6	NP_115810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF512	ENST00000355467.6	c.1367A>G	p.Lys456Arg	missense_variant	13/14	2	NM_032434.4	ENSP00000347648	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1256744 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 635096

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

May 01, 2023

The c.1367A>G (p.K456R) alteration is located in exon 13 (coding exon 13) of the ZNF512 gene. This alteration results from a A to G substitution at nucleotide position 1367, causing the lysine (K) at amino acid position 456 to be replaced by an arginine (R). 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	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	.;.;.;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;D;D;D
M_CAP	Benign	0.0049	T
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.90	.;.;.;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	.;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.067	.;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;.;.;.;D
Vest4		0.60
MutPred		0.68		.;.;.;.;Loss of ubiquitination at K456 (P = 0.0183);
MVP		0.18
MPC		1.3
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: 28

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: chr2-27840410;