9-111541677-A-G

Variant names:

• chr9-111541677-A-G
• rs1827672992
• NM_133464.5:c.742A>G

Variant summary

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

The NM_133464.5(ZNF483):​c.742A>G​(p.Ile248Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,068 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.160
• Publications: 0 publications found

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.051099837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133464.5. 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
	ZNF483	NM_133464.5	MANE Select	c.742A>G	p.Ile248Val	missense	Exon 6 of 6	NP_597721.2	Q8TF39-1
	ZNF483	NM_001007169.6		c.721+7324A>G		intron	N/A	NP_001007170.1	Q8TF39-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF483	ENST00000309235.6	TSL:1 MANE Select	c.742A>G	p.Ile248Val	missense	Exon 6 of 6	ENSP00000311679.5	Q8TF39-1
	ZNF483	ENST00000904413.1		c.742A>G	p.Ile248Val	missense	Exon 7 of 7	ENSP00000574477.1
	ZNF483	ENST00000904421.1		c.742A>G	p.Ile248Val	missense	Exon 7 of 7	ENSP00000574481.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451068 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721664

African (AFR) AF: 0.00 AC: 0 AN: 32576

American (AMR) AF: 0.00 AC: 0 AN: 41384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 83702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109256

Other (OTH) AF: 0.0000501 AC: 3 AN: 59872

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000375 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.16
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.028
Sift	Benign	0.68	T
Sift4G	Benign	0.80	T
Polyphen		0.012	B
Vest4		0.068
MVP		0.13
MPC		0.40
ClinPred		0.077	T
GERP RS		3.3
Varity_R		0.047
gMVP		0.034
Mutation Taster		=96/4	polymorphism

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: rs1827672992; hg19: chr9-114303957;