chr17-49298522-G-T

Variant names:

• chr17-49298522-G-T
• rs753274884
• NM_001145365.3:c.1712C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145365.3(ZNF652):​c.1712C>A​(p.Pro571Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P571L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF652 NM_001145365.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3852636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3	c.1712C>A	p.Pro571Gln	missense_variant	Exon 6 of 6	ENST00000430262.3	NP_001138837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF652	ENST00000430262.3	c.1712C>A	p.Pro571Gln	missense_variant	Exon 6 of 6	1	NM_001145365.3	ENSP00000416305.2
ZNF652	ENST00000362063.6	c.1712C>A	p.Pro571Gln	missense_variant	Exon 6 of 6	1		ENSP00000354686.2
ZNF652	ENST00000508237.5	n.1172C>A		non_coding_transcript_exon_variant	Exon 7 of 8	2		ENSP00000424848.1
FLJ40194	ENST00000655089.1	n.863+8026G>T		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	2.0	M;M
PhyloP100		5.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.47
MutPred		0.24		Loss of glycosylation at P571 (P = 0.036);Loss of glycosylation at P571 (P = 0.036);
MVP		0.37
MPC		1.1
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.37

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

Other links and lift over

dbSNP: rs753274884; hg19: chr17-47375884; COSMIC: COSV62947674;