chr7-64978144-T-A

Position:

• chr7-64978144-T-A

Variant summary

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

The NM_015852.5(ZNF117):​c.1427A>T​(p.Asp476Val) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF117 NM_015852.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.96

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 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=0.055152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2	c.1427A>T	p.Asp476Val	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5	c.1427A>T	p.Asp476Val	missense_variant	4/4		NP_056936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.1427A>T	p.Asp476Val	missense_variant	4/4	1		ENSP00000282869.5
ZNF117	ENST00000620222.4	c.1427A>T	p.Asp476Val	missense_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245592 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133234

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ESP6500AA AF: 0.000230 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000825 AC: 1

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 10, 2024

The c.1427A>T (p.D476V) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a A to T substitution at nucleotide position 1427, causing the aspartic acid (D) at amino acid position 476 to be replaced by a valine (V). 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	0.097
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.25	.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.026
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.045	D;D
Polyphen		0.0	B;B
Vest4		0.17
MVP		0.20
MPC		0.013
ClinPred		0.086	T
GERP RS		1.1
Varity_R		0.20
gMVP		0.0091

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: rs370821146; hg19: chr7-64438522;