NM_032434.4:c.461G>T

Variant names:

• chr2-27600694-G-T
• NM_032434.4:c.461G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032434.4(ZNF512):​c.461G>T​(p.Ser154Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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: 8.97
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4078071).

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.461G>T	p.Ser154Ile	missense	Exon 6 of 14	NP_115810.2
	ZNF512	NM_001271286.2		c.374G>T	p.Ser125Ile	missense	Exon 5 of 13	NP_001258215.1	Q96ME7-3
	ZNF512	NM_001271287.2		c.230G>T	p.Ser77Ile	missense	Exon 5 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.461G>T	p.Ser154Ile	missense	Exon 6 of 14	ENSP00000347648.3	Q96ME7-1
	ZNF512	ENST00000556601.5	TSL:1	c.230G>T	p.Ser77Ile	missense	Exon 5 of 13	ENSP00000451572.2	Q96ME7-2
	ZNF512	ENST00000879762.1		c.461G>T	p.Ser154Ile	missense	Exon 6 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PhyloP100		9.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.77
MutPred		0.40		Loss of helix (P = 0.0093)
MVP		0.26
MPC		0.64
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.51
gMVP		0.79
Mutation Taster		=57/43	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: chr2-27823561;