NM_032434.4:c.1310C>T

Variant names:

• chr2-27617486-C-T
• rs774844710
• NM_032434.4:c.1310C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032434.4(ZNF512):​c.1310C>T​(p.Ala437Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000309 in 1,292,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ZNF512 NM_032434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09037906).

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.1310C>T	p.Ala437Val	missense	Exon 13 of 14	NP_115810.2
	ZNF512	NM_001271286.2		c.1223C>T	p.Ala408Val	missense	Exon 12 of 13	NP_001258215.1	Q96ME7-3
	ZNF512	NM_001271287.2		c.1079C>T	p.Ala360Val	missense	Exon 12 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.1310C>T	p.Ala437Val	missense	Exon 13 of 14	ENSP00000347648.3	Q96ME7-1
	ZNF512	ENST00000556601.5	TSL:1	c.1079C>T	p.Ala360Val	missense	Exon 12 of 13	ENSP00000451572.2	Q96ME7-2
	ZNF512	ENST00000879762.1		c.1313C>T	p.Ala438Val	missense	Exon 13 of 14	ENSP00000549821.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251312 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000309 AC: 4 AN: 1292724 Hom.: 0 Cov.: 21 AF XY: 0.00000460 AC XY: 3 AN XY: 651836

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30250

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.0000771 AC: 3 AN: 38918

South Asian (SAS) AF: 0.00 AC: 0 AN: 82936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 957342

Other (OTH) AF: 0.00 AC: 0 AN: 54842

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00383038), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		3.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.14
Sift	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.59	P
Vest4		0.29
MutPred		0.48		Loss of sheet (P = 0.1158)
MVP		0.068
MPC		1.5
ClinPred		0.48	T
GERP RS		5.7
Varity_R		0.10
gMVP		0.33
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs774844710; hg19: chr2-27840353;