chr12-133151894-G-C

Position:

• chr12-133151894-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015394.5(ZNF10):​c.246G>C​(p.Glu82Asp) 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: ZNF10 NM_015394.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

Genes affected

ZNF10 (HGNC:12879): (zinc finger protein 10) The protein encoded by this gene contains a C2H2 zinc finger, and has been shown to function as a transcriptional repressor. The Kruppel-associated box (KRAB) domain of this protein is found to be responsible for its transcriptional repression activity. RING finger containing protein TIF1 was reported to interact with the KRAB domain, and may serve as a mediator for the repression activity of this protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049770653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF10	NM_015394.5	c.246G>C	p.Glu82Asp	missense_variant	4/5	ENST00000248211.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF10	ENST00000248211.11	c.246G>C	p.Glu82Asp	missense_variant	4/5	1	NM_015394.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.018	T;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.57	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.012
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.039	B;B;.;.
Vest4		0.11
MutPred		0.30		Gain of catalytic residue at E78 (P = 0.0127);Gain of catalytic residue at E78 (P = 0.0127);Gain of catalytic residue at E78 (P = 0.0127);Gain of catalytic residue at E78 (P = 0.0127);
MVP		0.29
MPC		0.15
ClinPred		0.10	T
GERP RS		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.075
gMVP		0.031

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: rs1956010440; hg19: chr12-133728480;