17-49316984-C-T

Variant names:

• chr17-49316984-C-T
• rs1056101745
• NM_001145365.3:c.742G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145365.3(ZNF652):​c.742G>A​(p.Glu248Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF652 NM_001145365.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

Genes affected

ZNF652 (HGNC:29147): (zinc finger protein 652) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FLJ40194 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38800934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3	c.742G>A	p.Glu248Lys	missense_variant	Exon 2 of 6	ENST00000430262.3	NP_001138837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF652	ENST00000430262.3	c.742G>A	p.Glu248Lys	missense_variant	Exon 2 of 6	1	NM_001145365.3	ENSP00000416305.2
ZNF652	ENST00000362063.6	c.742G>A	p.Glu248Lys	missense_variant	Exon 2 of 6	1		ENSP00000354686.2
ZNF652	ENST00000508237.5	n.360+382G>A		intron_variant	Intron 3 of 7	2		ENSP00000424848.1
FLJ40194	ENST00000655089.1	n.864-607C>T		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.742G>A (p.E248K) alteration is located in exon 2 (coding exon 1) of the ZNF652 gene. This alteration results from a G to A substitution at nucleotide position 742, causing the glutamic acid (E) at amino acid position 248 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	0.33
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.14
Sift	Benign	0.62	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.86	P;P
Vest4		0.64
MutPred		0.42		Gain of methylation at E248 (P = 0);Gain of methylation at E248 (P = 0);
MVP		0.082
MPC		0.46
ClinPred		0.79	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.50

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: rs1056101745; hg19: chr17-47394346;