rs201225007

Variant names:

• chr17-34961694-C-G
• rs201225007
• NM_052857.4:c.128C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-34961694-C-G
• chr17-34961694-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052857.4(ZNF830):​c.128C>G​(p.Ala43Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A43V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF830 NM_052857.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF830	NM_052857.4	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 1	ENST00000361952.5	NP_443089.3
CCT6B	NM_006584.4	c.-301G>C		upstream_gene_variant		ENST00000314144.10	NP_006575.2
CCT6B	NM_001193529.3	c.-301G>C		upstream_gene_variant			NP_001180458.1
CCT6B	NM_001193530.2	c.-301G>C		upstream_gene_variant			NP_001180459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF830	ENST00000361952.5	c.128C>G	p.Ala43Gly	missense_variant	Exon 1 of 1	6	NM_052857.4	ENSP00000354518.3
CCT6B	ENST00000585073.1	c.-90-7095G>C		intron_variant	Intron 1 of 4	3		ENSP00000462020.1
CCT6B	ENST00000314144.10	c.-301G>C		upstream_gene_variant		1	NM_006584.4	ENSP00000327191.5
CCT6B	ENST00000436961.7	c.-301G>C		upstream_gene_variant		2		ENSP00000400917.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.59		Loss of stability (P = 0.0776);
MVP		0.37
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs201225007; hg19: chr17-33288713;