7-64978670-C-T

Position:

• chr7-64978670-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.901G>A​(p.Gly301Arg) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF117 NM_015852.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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]

ERV3-1-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=0.17031261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF117	NM_015852.5	c.901G>A	p.Gly301Arg	missense_variant	4/4	ENST00000282869.11	NP_056936.2
ERV3-1-ZNF117	NM_001348050.2	c.901G>A	p.Gly301Arg	missense_variant	4/4		NP_001334979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.901G>A	p.Gly301Arg	missense_variant	4/4	1	NM_015852.5	ENSP00000282869	P1
ZNF117	ENST00000620222.4	c.901G>A	p.Gly301Arg	missense_variant	3/3	1		ENSP00000479944	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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 19, 2024

The c.901G>A (p.G301R) 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 901, causing the glycine (G) at amino acid position 301 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	Benign	0.21
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.18	.;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.90	D
PROVEAN	Pathogenic	-5.5	D;.
REVEL	Benign	0.038
Sift	Benign	0.030	D;.
Sift4G	Uncertain	0.022	D;D
Polyphen		0.80	P;P
Vest4		0.073
MutPred		0.48		Loss of ubiquitination at K303 (P = 0.0298);Loss of ubiquitination at K303 (P = 0.0298);
MVP		0.37
MPC		0.091
ClinPred		0.89	D
GERP RS		1.3
Varity_R		0.14
gMVP		0.0094

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: rs1785954292; hg19: chr7-64439048;