17-34962185-A-G

Position:

• chr17-34962185-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_052857.4(ZNF830):​c.619A>G​(p.Asn207Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,108 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: ZNF830 NM_052857.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011175215).
• BP6: Variant 17-34962185-A-G is Benign according to our data. Variant chr17-34962185-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2457451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF830	NM_052857.4	c.619A>G	p.Asn207Asp	missense_variant	1/1	ENST00000361952.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF830	ENST00000361952.5	c.619A>G	p.Asn207Asp	missense_variant	1/1		NM_052857.4	P1
CCT6B	ENST00000585073.1	c.-90-7586T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000255 AC: 64 AN: 250642 Hom.: 0 AF XY: 0.000280 AC XY: 38 AN XY: 135706

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000336

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1461792 Hom.: 3 Cov.: 33 AF XY: 0.000184 AC XY: 134 AN XY: 727196

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.000447

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74486

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000352 Hom.: 1

Bravo AF: 0.000147

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.43
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.0060
Sift	Benign	0.62	T
Sift4G	Benign	0.33	T
Polyphen		0.0020	B
Vest4		0.028
MVP		0.095
MPC		0.45
ClinPred		0.0057	T
GERP RS		-4.3
Varity_R		0.052
gMVP		0.035

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: rs138219937; hg19: chr17-33289204; COSMIC: COSV58489221; COSMIC: COSV58489221;