rs2560306

Variant names:

• chr5-122152508-G-A
• rs2560306
• NM_207317.3:c.518G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-122152508-G-A
• chr5-122152508-G-T

Variant summary

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

The NM_207317.3(ZNF474):​c.518G>A​(p.Arg173His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,613,948 control chromosomes in the GnomAD database, including 5,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1880 hom., cov: 32)
  • Exomes 𝑓: 0.055 (3468 hom.)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• Publications: 11 publications found

Genes affected

ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF475 (HGNC:53564): (zinc finger protein 475)

ENSG00000247311 (HGNC:):

ZNF474-AS1 (HGNC:41019): (ZNF474 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050495863).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207317.3. 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
	ZNF474	NM_207317.3	MANE Select	c.518G>A	p.Arg173His	missense	Exon 2 of 2	NP_997200.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF474	ENST00000296600.5	TSL:1 MANE Select	c.518G>A	p.Arg173His	missense	Exon 2 of 2	ENSP00000296600.4
	ZNF474	ENST00000698749.1		c.518G>A	p.Arg173His	missense	Exon 2 of 4	ENSP00000513911.1
	ZNF474	ENST00000698748.1		c.518G>A	p.Arg173His	missense	Exon 2 of 6	ENSP00000513910.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17839 AN: 151978 Hom.: 1875 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0592

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0989

GnomAD2 exomes AF: 0.0708 AC: 17735 AN: 250524 AF XY: 0.0668

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.0347

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0433

Gnomad OTH exome AF: 0.0567

GnomAD4 exome AF: 0.0548 AC: 80077 AN: 1461852 Hom.: 3468 Cov.: 31 AF XY: 0.0544 AC XY: 39562 AN XY: 727226

African (AFR) AF: 0.296 AC: 9926 AN: 33480

American (AMR) AF: 0.0376 AC: 1682 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0301 AC: 787 AN: 26134

East Asian (EAS) AF: 0.0836 AC: 3319 AN: 39698

South Asian (SAS) AF: 0.0618 AC: 5332 AN: 86256

European-Finnish (FIN) AF: 0.0987 AC: 5273 AN: 53398

Middle Eastern (MID) AF: 0.0546 AC: 315 AN: 5768

European-Non Finnish (NFE) AF: 0.0445 AC: 49479 AN: 1112004

Other (OTH) AF: 0.0656 AC: 3964 AN: 60394

GnomAD4 genome AF: 0.118 AC: 17874 AN: 152096 Hom.: 1880 Cov.: 32 AF XY: 0.119 AC XY: 8858 AN XY: 74350

African (AFR) AF: 0.281 AC: 11640 AN: 41458

American (AMR) AF: 0.0591 AC: 903 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3466

East Asian (EAS) AF: 0.0992 AC: 512 AN: 5160

South Asian (SAS) AF: 0.0638 AC: 307 AN: 4814

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3016 AN: 68014

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0607 Hom.: 2195

Bravo AF: 0.122

TwinsUK AF: 0.0399 AC: 148

ALSPAC AF: 0.0420 AC: 162

ESP6500AA AF: 0.281 AC: 1239

ESP6500EA AF: 0.0435 AC: 374

ExAC AF: 0.0747 AC: 9067

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.86
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.33
Sift	Benign	0.036	D
Sift4G	Uncertain	0.038	D
Polyphen		0.15	B
Vest4		0.11
MPC		0.0036
ClinPred		0.093	T
GERP RS		0.80
Varity_R		0.27
gMVP		0.20
Mutation Taster		=99/1	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: rs2560306; hg19: chr5-121488203; COSMIC: COSV56945499; COSMIC: COSV56945499;