17-34961570-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity ZN830_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40140855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF830	NM_052857.4	c.4G>T	p.Ala2Ser	missense_variant	Exon 1 of 1	ENST00000361952.5	NP_443089.3
CCT6B	NM_006584.4	c.-177C>A		upstream_gene_variant		ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.-177C>A		upstream_gene_variant			NP_001180458.1
CCT6B	NM_001193530.2	c.-177C>A		upstream_gene_variant			NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF830	ENST00000361952.5	c.4G>T	p.Ala2Ser	missense_variant	Exon 1 of 1	6	NM_052857.4	ENSP00000354518.3
CCT6B	ENST00000314144.10	c.-177C>A		upstream_gene_variant		1	NM_006584.4	ENSP00000327191.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4G>T (p.A2S) alteration is located in exon 1 (coding exon 1) of the ZNF830 gene. This alteration results from a G to T substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a serine (S). 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	0.10
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
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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33288589;