chr2-27607872-C-T

Variant names:

• chr2-27607872-C-T
• NM_032434.4:c.964C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032434.4(ZNF512):​c.964C>T​(p.Pro322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P322L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF512 NM_032434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.309
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050692856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032434.4. 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
	ZNF512	NM_032434.4	MANE Select	c.964C>T	p.Pro322Ser	missense	Exon 10 of 14	NP_115810.2
	ZNF512	NM_001271286.2		c.877C>T	p.Pro293Ser	missense	Exon 9 of 13	NP_001258215.1	Q96ME7-3
	ZNF512	NM_001271287.2		c.733C>T	p.Pro245Ser	missense	Exon 9 of 13	NP_001258216.1	Q96ME7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF512	ENST00000355467.6	TSL:2 MANE Select	c.964C>T	p.Pro322Ser	missense	Exon 10 of 14	ENSP00000347648.3	Q96ME7-1
	ZNF512	ENST00000556601.5	TSL:1	c.733C>T	p.Pro245Ser	missense	Exon 9 of 13	ENSP00000451572.2	Q96ME7-2
	ZNF512	ENST00000879762.1		c.964C>T	p.Pro322Ser	missense	Exon 10 of 14	ENSP00000549821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.31
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.045
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.27		Gain of phosphorylation at P322 (P = 0.0388)
MVP		0.043
MPC		0.54
ClinPred		0.094	T
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.23
Mutation Taster		=75/25	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: chr2-27830739;