chr17-34961570-G-T

Variant names:

• chr17-34961570-G-T
• NM_052857.4:c.4G>T

Variant summary

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

The NM_052857.4(ZNF830):​c.4G>T​(p.Ala2Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF830 NM_052857.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38
• Publications: 0 publications found

Genes affected

ZNF830 (HGNC:28291): (zinc finger protein 830) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in several processes, including DNA-dependent DNA replication; mitotic DNA integrity checkpoint signaling; and preantral ovarian follicle growth. Predicted to act upstream of or within several processes, including blastocyst growth; chromosome organization; and intestinal epithelial structure maintenance. Predicted to be located in nucleoplasm. Predicted to be part of spliceosomal complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCT6B (HGNC:1621): (chaperonin containing TCP1 subunit 6B) This gene encodes a molecular chaperone that is a member of the chaperonin-containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

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=0.40140855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052857.4. 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
	ZNF830	NM_052857.4	MANE Select	c.4G>T	p.Ala2Ser	missense	Exon 1 of 1	NP_443089.3
	CCT6B	NM_006584.4	MANE Select	c.-177C>A		upstream_gene	N/A	NP_006575.2	Q92526-1
	CCT6B	NM_001193529.3		c.-177C>A		upstream_gene	N/A	NP_001180458.1	Q92526-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF830	ENST00000361952.5	TSL:6 MANE Select	c.4G>T	p.Ala2Ser	missense	Exon 1 of 1	ENSP00000354518.3	Q96NB3
	CCT6B	ENST00000585073.1	TSL:3	c.-90-6971C>A		intron	N/A	ENSP00000462020.1	J3KRI6
	CCT6B	ENST00000314144.10	TSL:1 MANE Select	c.-177C>A		upstream_gene	N/A	ENSP00000327191.5	Q92526-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.17
Sift	Benign	0.073	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.24		Gain of phosphorylation at A2 (P = 0.0023)
MVP		0.21
MPC		0.37
ClinPred		0.88	D
GERP RS		5.4
PromoterAI		-0.55	Under-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.56

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

hg19: chr17-33288589;