chr17-34962107-A-T

Variant names:

• chr17-34962107-A-T
• rs932468622
• NM_052857.4:c.541A>T

Variant summary

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

The NM_052857.4(ZNF830):​c.541A>T​(p.Ser181Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S181T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF830 NM_052857.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.248
• 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: 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=0.054304868).

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.541A>T	p.Ser181Cys	missense	Exon 1 of 1	NP_443089.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF830	ENST00000361952.5	TSL:6 MANE Select	c.541A>T	p.Ser181Cys	missense	Exon 1 of 1	ENSP00000354518.3	Q96NB3
	CCT6B	ENST00000585073.1	TSL:3	c.-90-7508T>A		intron	N/A	ENSP00000462020.1	J3KRI6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250816 AF XY: 0.00000737

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461808 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000501 Hom.: 0

Bravo AF: 0.00000756

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	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.036
Sift	Benign	0.060	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0020	B
Vest4		0.058
MutPred		0.21		Loss of phosphorylation at S181 (P = 0.0054)
MVP		0.048
MPC		0.38
ClinPred		0.052	T
GERP RS		1.9
Varity_R		0.062
gMVP		0.095

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: rs932468622; hg19: chr17-33289126;