chr17-49316930-C-G

Variant names:

• chr17-49316930-C-G
• rs374441735
• NM_001145365.3:c.796G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001145365.3(ZNF652):​c.796G>C​(p.Val266Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V266I) 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: 7.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3	c.796G>C	p.Val266Leu	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.796G>C	p.Val266Leu	missense_variant	Exon 2 of 6	1	NM_001145365.3	ENSP00000416305.2
ZNF652	ENST00000362063.6	c.796G>C	p.Val266Leu	missense_variant	Exon 2 of 6	1		ENSP00000354686.2
ZNF652	ENST00000508237.5	n.360+436G>C		intron_variant	Intron 3 of 7	2		ENSP00000424848.1
FLJ40194	ENST00000655089.1	n.864-661C>G		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	.;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		7.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.67		Loss of MoRF binding (P = 0.1101);Loss of MoRF binding (P = 0.1101);
MVP		0.44
MPC		1.2
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.55
gMVP		0.49

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

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Other links and lift over

dbSNP: rs374441735; hg19: chr17-47394292;