9-106914612-A-G

Variant names:

• chr9-106914612-A-G
• rs1858231
• NM_021224.6:c.-30-8742A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021224.6(ZNF462):​c.-30-8742A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,076 control chromosomes in the GnomAD database, including 9,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9504 hom., cov: 32)
• Consequence: ZNF462 NM_021224.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 9 publications found

Genes affected

ZNF462 (HGNC:21684): (zinc finger protein 462) The protein encoded by this gene belongs to C2H2-type zinc finger family of proteins. It contains multiple C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ZNF462 Gene-Disease associations (from GenCC):

• Weiss-Kruszka syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021224.6. 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
	ZNF462	NM_021224.6	MANE Select	c.-30-8742A>G		intron	N/A	NP_067047.4
	ZNF462	NM_001347997.2		c.-30-8742A>G		intron	N/A	NP_001334926.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF462	ENST00000277225.10	TSL:1 MANE Select	c.-30-8742A>G		intron	N/A	ENSP00000277225.5	Q96JM2-1
	ZNF462	ENST00000902271.1		c.-30-8742A>G		intron	N/A	ENSP00000572330.1
	ZNF462	ENST00000472574.1	TSL:4	c.-30-8742A>G		intron	N/A	ENSP00000476222.1	U3KQU3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47079 AN: 151958 Hom.: 9498 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47122 AN: 152076 Hom.: 9504 Cov.: 32 AF XY: 0.305 AC XY: 22685 AN XY: 74328

African (AFR) AF: 0.567 AC: 23510 AN: 41452

American (AMR) AF: 0.302 AC: 4609 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1825 AN: 5160

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10572

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12983 AN: 68002

Other (OTH) AF: 0.305 AC: 643 AN: 2110

Alfa AF: 0.232 Hom.: 9176

Bravo AF: 0.333

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs1858231; hg19: chr9-109676893;