chr17-49298627-C-T

Variant names:

• chr17-49298627-C-T
• rs371960327
• NM_001145365.3:c.1607G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145365.3(ZNF652):​c.1607G>A​(p.Ser536Asn) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF652 NM_001145365.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.697
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04134327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF652	NM_001145365.3	MANE Select	c.1607G>A	p.Ser536Asn	missense	Exon 6 of 6	NP_001138837.1	Q9Y2D9
	ZNF652	NM_014897.2		c.1607G>A	p.Ser536Asn	missense	Exon 6 of 6	NP_055712.1	Q9Y2D9
	ZNF652	NR_135579.2		n.1791G>A		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF652	ENST00000430262.3	TSL:1 MANE Select	c.1607G>A	p.Ser536Asn	missense	Exon 6 of 6	ENSP00000416305.2	Q9Y2D9
	ZNF652	ENST00000362063.6	TSL:1	c.1607G>A	p.Ser536Asn	missense	Exon 6 of 6	ENSP00000354686.2	Q9Y2D9
	ZNF652	ENST00000949719.1		c.1661G>A	p.Ser554Asn	missense	Exon 7 of 7	ENSP00000619778.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249006 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.70
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.17
Sift	Benign	0.37	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.29		Loss of glycosylation at S536 (P = 5e-04)
MVP		0.068
MPC		0.36
ClinPred		0.14	T
GERP RS		2.3
Varity_R		0.042
gMVP		0.099

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: rs371960327; hg19: chr17-47375989; COSMIC: COSV105282459;