chr7-149250304-C-G

Position:

• chr7-149250304-C-G

Variant summary

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

The NM_012256.4(ZNF212):​c.170C>G​(p.Ser57Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF212 NM_012256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819

Genes affected

ZNF212 (HGNC:13004): (zinc finger protein 212) This gene belongs to the C2H2-type zinc finger gene family. The zinc finger proteins are involved in gene regulation and development, and are quite conserved throughout evolution. Like this gene product, a third of the zinc finger proteins containing C2H2 fingers also contain the KRAB domain, which has been found to be involved in protein-protein interactions. [provided by RefSeq, Jul 2008]

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=0.19184029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF212	NM_012256.4	c.170C>G	p.Ser57Cys	missense_variant	2/5	ENST00000335870.7	NP_036388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF212	ENST00000335870.7	c.170C>G	p.Ser57Cys	missense_variant	2/5	1	NM_012256.4	ENSP00000338572.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 10, 2024

The c.170C>G (p.S57C) alteration is located in exon 2 (coding exon 2) of the ZNF212 gene. This alteration results from a C to G substitution at nucleotide position 170, causing the serine (S) at amino acid position 57 to be replaced by a cysteine (C). 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	0.17
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.32
Sift	Benign	0.056	T
Sift4G	Benign	0.084	T
Polyphen		0.98	D
Vest4		0.30
MVP		0.84
MPC		0.73
ClinPred		0.97	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs1796733902; hg19: chr7-148947395;