7-149253634-G-A

Position:

• chr7-149253634-G-A

Variant summary

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

The NM_012256.4(ZNF212):​c.707G>A​(p.Cys236Tyr) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF212 NM_012256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.577

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=0.081921875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF212	NM_012256.4	c.707G>A	p.Cys236Tyr	missense_variant	5/5	ENST00000335870.7	NP_036388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF212	ENST00000335870.7	c.707G>A	p.Cys236Tyr	missense_variant	5/5	1	NM_012256.4	ENSP00000338572	P1
ZNF212	ENST00000481584.1	c.449G>A	p.Cys150Tyr	missense_variant	5/5	3		ENSP00000419419
ZNF212	ENST00000488917.1	c.*174G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	4		ENSP00000419261

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 23, 2023

The c.707G>A (p.C236Y) alteration is located in exon 5 (coding exon 5) of the ZNF212 gene. This alteration results from a G to A substitution at nucleotide position 707, causing the cysteine (C) at amino acid position 236 to be replaced by a tyrosine (Y). 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	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.64
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.061
Sift	Benign	0.55	T
Sift4G	Benign	0.089	T
Polyphen		0.0010	B
Vest4		0.087
MutPred		0.66		Gain of phosphorylation at C236 (P = 0.0201);
MVP		0.16
MPC		0.40
ClinPred		0.027	T
GERP RS		0.72
Varity_R		0.024
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-148950725;