2-27607899-G-C

Variant names:

• chr2-27607899-G-C
• rs1672441738
• NM_032434.4:c.991G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032434.4(ZNF512):​c.991G>C​(p.Glu331Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZNF512 NM_032434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

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]

ENSG00000259080 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19305667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF512	NM_032434.4	c.991G>C	p.Glu331Gln	missense_variant	Exon 10 of 14	ENST00000355467.6	NP_115810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF512	ENST00000355467.6	c.991G>C	p.Glu331Gln	missense_variant	Exon 10 of 14	2	NM_032434.4	ENSP00000347648.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.991G>C (p.E331Q) alteration is located in exon 10 (coding exon 10) of the ZNF512 gene. This alteration results from a G to C substitution at nucleotide position 991, causing the glutamic acid (E) at amino acid position 331 to be replaced by a glutamine (Q). 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	Benign	0.12
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;.;.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D;D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	.;.;.;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	.;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.031	.;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		0.94	.;.;.;.;P
Vest4		0.35
MutPred		0.41		.;.;.;.;Loss of ubiquitination at K333 (P = 0.0226);
MVP		0.20
MPC		0.53
ClinPred		0.93	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1672441738; hg19: chr2-27830766;