chr7-64978834-T-C

Position:

• chr7-64978834-T-C

Variant summary

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

The NM_015852.5(ZNF117):​c.737A>G​(p.Glu246Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 1.66

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.737A>G	p.Glu246Gly	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5	c.737A>G	p.Glu246Gly	missense_variant	4/4		NP_056936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.737A>G	p.Glu246Gly	missense_variant	4/4	1		ENSP00000282869.5
ZNF117	ENST00000620222.4	c.737A>G	p.Glu246Gly	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

Oct 09, 2024

The c.737A>G (p.E246G) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a A to G substitution at nucleotide position 737, causing the glutamic acid (E) at amino acid position 246 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;T;.
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.067	.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;L;.
PROVEAN	Pathogenic	-6.1	D;.;.
REVEL	Benign	0.11
Sift	Benign	0.049	D;.;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.11
MutPred		0.65		Loss of ubiquitination at K247 (P = 0.0982);Loss of ubiquitination at K247 (P = 0.0982);Loss of ubiquitination at K247 (P = 0.0982);
MVP		0.38
MPC		0.057
ClinPred		0.97	D
GERP RS		1.2
Varity_R		0.14
gMVP		0.0084

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: chr7-64439212;