chr7-64978942-G-T

Position:

• chr7-64978942-G-T

Variant summary

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

The NM_015852.5(ZNF117):​c.629C>A​(p.Thr210Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF117 NM_015852.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.92

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 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=0.0653519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF117	NM_015852.5	c.629C>A	p.Thr210Lys	missense_variant	4/4	ENST00000282869.11	NP_056936.2
ERV3-1-ZNF117	NM_001348050.2	c.629C>A	p.Thr210Lys	missense_variant	4/4		NP_001334979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11	c.629C>A	p.Thr210Lys	missense_variant	4/4	1	NM_015852.5	ENSP00000282869	P1
ZNF117	ENST00000620222.4	c.629C>A	p.Thr210Lys	missense_variant	3/3	1		ENSP00000479944	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461322 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 726958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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 10, 2024

The c.629C>A (p.T210K) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a C to A substitution at nucleotide position 629, causing the threonine (T) at amino acid position 210 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.024
DANN	Benign	0.74
DEOGEN2	Benign	0.0032	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.0091	.;T;T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.0	N;N;.
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.064
Sift	Benign	0.81	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0070	B;B;.
Vest4		0.048
MutPred		0.51		Gain of methylation at T210 (P = 0.0163);Gain of methylation at T210 (P = 0.0163);Gain of methylation at T210 (P = 0.0163);
MVP		0.13
MPC		0.013
ClinPred		0.060	T
GERP RS		-2.4
Varity_R		0.027
gMVP		0.012

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: rs372088616; hg19: chr7-64439320;