NM_012256.4:c.373A>G

Variant names:

• chr7-149250507-A-G
• rs1467915998
• NM_012256.4:c.373A>G

Variant summary

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

The NM_012256.4(ZNF212):​c.373A>G​(p.Ile125Val) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I125F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF212 NM_012256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 0 publications found

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

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=0.030262887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012256.4. 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
	ZNF212	NM_012256.4	MANE Select	c.373A>G	p.Ile125Val	missense	Exon 2 of 5	NP_036388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF212	ENST00000335870.7	TSL:1 MANE Select	c.373A>G	p.Ile125Val	missense	Exon 2 of 5	ENSP00000338572.2	Q9UDV6
	ZNF212	ENST00000877956.1		c.373A>G	p.Ile125Val	missense	Exon 2 of 5	ENSP00000548015.1
	ZNF212	ENST00000481584.1	TSL:3	c.64A>G	p.Ile22Val	missense	Exon 1 of 5	ENSP00000419419.1	H7C5A9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.52	N
PhyloP100		-0.32
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.049
Sift	Benign	0.30	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.38		Gain of disorder (P = 0.079)
MVP		0.10
MPC		0.18
ClinPred		0.040	T
GERP RS		-0.71
PromoterAI		-0.031	Neutral
Varity_R		0.020
gMVP		0.069
Mutation Taster		=95/5	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

dbSNP: rs1467915998; hg19: chr7-148947598;