chr9-111533745-A-G

Variant names:

• chr9-111533745-A-G
• rs150435163
• NM_133464.5:c.508A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_133464.5(ZNF483):​c.508A>G​(p.Ile170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,563,986 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059120357).
• BP6: Variant 9-111533745-A-G is Benign according to our data. Variant chr9-111533745-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2392204.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF483	NM_133464.5	c.508A>G	p.Ile170Val	missense_variant	Exon 4 of 6	ENST00000309235.6	NP_597721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF483	ENST00000309235.6	c.508A>G	p.Ile170Val	missense_variant	Exon 4 of 6	1	NM_133464.5	ENSP00000311679.5
ZNF483	ENST00000355824.7	c.508A>G	p.Ile170Val	missense_variant	Exon 4 of 6	1		ENSP00000438048.1
ZNF483	ENST00000358151.8	c.508A>G	p.Ile170Val	missense_variant	Exon 4 of 6	2		ENSP00000350871.4

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00154

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000690 AC: 14 AN: 202850 AF XY: 0.0000720

Gnomad AFR exome AF: 0.000863

Gnomad AMR exome AF: 0.0000499

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000439 AC: 62 AN: 1411646 Hom.: 0 Cov.: 31 AF XY: 0.0000356 AC XY: 25 AN XY: 701724

African (AFR) AF: 0.00189 AC: 56 AN: 29566

American (AMR) AF: 0.0000339 AC: 1 AN: 29510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23956

East Asian (EAS) AF: 0.00 AC: 0 AN: 37728

South Asian (SAS) AF: 0.00 AC: 0 AN: 76866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1097174

Other (OTH) AF: 0.00 AC: 0 AN: 58184

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74486

African (AFR) AF: 0.00154 AC: 64 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000438 Hom.: 0

Bravo AF: 0.000465

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 02, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.11
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.053
DANN	Benign	0.19
DEOGEN2	Benign	0.00052	.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.0059	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N;.;N
PhyloP100		-0.30
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.29	N;N;N
REVEL	Benign	0.029
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0, 0.0010	.;B;B
Vest4		0.040
MVP		0.081
MPC		0.45
ClinPred		0.0052	T
GERP RS		-4.5
Varity_R		0.023
gMVP		0.046
Mutation Taster		=94/6	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: rs150435163; hg19: chr9-114296025;