7-64978351-C-T

Position:

• chr7-64978351-C-T

Variant summary

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

The NM_015852.5(ZNF117):​c.1220G>A​(p.Cys407Tyr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZNF117 NM_015852.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10975799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2	c.1220G>A	p.Cys407Tyr	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5	c.1220G>A	p.Cys407Tyr	missense_variant	4/4		NP_056936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.1220G>A	p.Cys407Tyr	missense_variant	4/4	1		ENSP00000282869.5
ZNF117	ENST00000620222.4	c.1220G>A	p.Cys407Tyr	missense_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 142886 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 56

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000700 AC: 1 AN: 142886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 69648

Gnomad4 AFR AF: 0.0000261

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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 11, 2024

The c.1220G>A (p.C407Y) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a G to A substitution at nucleotide position 1220, causing the cysteine (C) at amino acid position 407 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	0.085
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.38
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.13	.;T
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.24	N;N
PROVEAN	Benign	4.3	N;.
REVEL	Benign	0.071
Sift	Uncertain	0.014	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0010	B;B
Vest4		0.11
MutPred		0.38		Loss of methylation at K408 (P = 0.0285);Loss of methylation at K408 (P = 0.0285);
MVP		0.081
MPC		0.013
ClinPred		0.085	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.014

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: rs1214131123; hg19: chr7-64438729;