chr10-43616797-G-A

Variant names:

• chr10-43616797-G-A
• rs12354886
• NM_145312.4:c.754G>A

Variant summary

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

The NM_145312.4(ZNF485):​c.754G>A​(p.Ala252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,688 control chromosomes in the GnomAD database, including 42,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4025 hom., cov: 33)
  • Exomes 𝑓: 0.22 (38137 hom.)
• Consequence: ZNF485 NM_145312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 24 publications found

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046267807).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF485	NM_145312.4	c.754G>A	p.Ala252Thr	missense_variant	Exon 5 of 5	ENST00000361807.8	NP_660355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF485	ENST00000361807.8	c.754G>A	p.Ala252Thr	missense_variant	Exon 5 of 5	1	NM_145312.4	ENSP00000354694.3
ZNF485	ENST00000374435.3	c.754G>A	p.Ala252Thr	missense_variant	Exon 5 of 5	1		ENSP00000363558.3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34089 AN: 151846 Hom.: 4023 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.224

GnomAD2 exomes AF: 0.193 AC: 48508 AN: 251072 AF XY: 0.193

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.000925

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.223 AC: 325407 AN: 1461726 Hom.: 38137 Cov.: 38 AF XY: 0.222 AC XY: 161147 AN XY: 727156

African (AFR) AF: 0.269 AC: 9017 AN: 33478

American (AMR) AF: 0.164 AC: 7348 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5601 AN: 26134

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39694

South Asian (SAS) AF: 0.186 AC: 16039 AN: 86254

European-Finnish (FIN) AF: 0.164 AC: 8751 AN: 53352

Middle Eastern (MID) AF: 0.178 AC: 1026 AN: 5768

European-Non Finnish (NFE) AF: 0.238 AC: 264467 AN: 1111942

Other (OTH) AF: 0.217 AC: 13132 AN: 60384

GnomAD4 genome AF: 0.224 AC: 34110 AN: 151962 Hom.: 4025 Cov.: 33 AF XY: 0.217 AC XY: 16123 AN XY: 74280

African (AFR) AF: 0.273 AC: 11296 AN: 41448

American (AMR) AF: 0.201 AC: 3075 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3470

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5138

South Asian (SAS) AF: 0.187 AC: 898 AN: 4810

European-Finnish (FIN) AF: 0.150 AC: 1582 AN: 10566

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15873 AN: 67936

Other (OTH) AF: 0.222 AC: 469 AN: 2112

Alfa AF: 0.226 Hom.: 13854

Bravo AF: 0.228

TwinsUK AF: 0.240 AC: 890

ALSPAC AF: 0.234 AC: 900

ESP6500AA AF: 0.268 AC: 1183

ESP6500EA AF: 0.232 AC: 1995

ExAC AF: 0.196 AC: 23788

Asia WGS AF: 0.0920 AC: 321 AN: 3478

EpiCase AF: 0.230

EpiControl AF: 0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.67
DEOGEN2	Benign	0.0044	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00023	N
LIST_S2	Benign	0.16	.;T
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.95	N;N
PhyloP100		0.45
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.29	N;N
REVEL	Benign	0.012
Sift	Benign	0.61	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0010	B;B
Vest4		0.018
MPC		0.12
ClinPred		0.00018	T
GERP RS		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.012
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: rs12354886; hg19: chr10-44112245; COSMIC: COSV62425571; COSMIC: COSV62425571;