7-64978904-A-G

Position:

• chr7-64978904-A-G

Variant summary

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

The NM_015852.5(ZNF117):​c.667T>C​(p.Cys223Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF117 NM_015852.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57

Genes affected

ZNF117 (HGNC:12897): (zinc finger protein 117) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Readthrough transcription occurs between this gene and the upstream endogenous retrovirus group 3 member 1 (ERV3-1) locus, and may result in additional transcript variants encoding the zinc finger protein. [provided by RefSeq, Jan 2017]

ZNF117 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2	c.667T>C	p.Cys223Arg	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5	c.667T>C	p.Cys223Arg	missense_variant	4/4		NP_056936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.667T>C	p.Cys223Arg	missense_variant	4/4	1		ENSP00000282869.5
ZNF117	ENST00000620222.4	c.667T>C	p.Cys223Arg	missense_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 33

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

Nov 25, 2024

The c.667T>C (p.C223R) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a T to C substitution at nucleotide position 667, causing the cysteine (C) at amino acid position 223 to be replaced by an arginine (R). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.36	T;T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	-0.076
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.17	.;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.9	H;H;.
PROVEAN	Pathogenic	-10	D;.;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.26
MutPred		0.72		Gain of MoRF binding (P = 0.0284);Gain of MoRF binding (P = 0.0284);Gain of MoRF binding (P = 0.0284);
MVP		0.57
MPC		0.091
ClinPred		0.86	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
gMVP		0.067

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: chr7-64439282;