5-122152811-C-G

Variant names:

• chr5-122152811-C-G
• rs35262183
• NM_207317.3:c.821C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207317.3(ZNF474):​c.821C>G​(p.Ser274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,613,954 control chromosomes in the GnomAD database, including 68,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.24 (5033 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63620 hom.)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

Genes affected

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

ENSG00000250803 (HGNC:53564): (zinc finger protein 475)

ENSG00000247311 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017801821).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF474	NM_207317.3	c.821C>G	p.Ser274Cys	missense_variant	Exon 2 of 2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1	n.271+1813G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5	c.821C>G	p.Ser274Cys	missense_variant	Exon 2 of 2	1	NM_207317.3	ENSP00000296600.4

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36749 AN: 151978 Hom.: 5039 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.287 AC: 72206 AN: 251252 Hom.: 10933 AF XY: 0.296 AC XY: 40139 AN XY: 135784

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.291 AC: 424986 AN: 1461858 Hom.: 63620 Cov.: 64 AF XY: 0.294 AC XY: 213972 AN XY: 727220

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.241 AC: 36729 AN: 152096 Hom.: 5033 Cov.: 32 AF XY: 0.248 AC XY: 18469 AN XY: 74336

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.239

Alfa AF: 0.287 Hom.: 4863

Bravo AF: 0.227

TwinsUK AF: 0.285 AC: 1056

ALSPAC AF: 0.286 AC: 1104

ESP6500AA AF: 0.116 AC: 512

ESP6500EA AF: 0.282 AC: 2424

ExAC AF: 0.286 AC: 34695

Asia WGS AF: 0.293 AC: 1020 AN: 3478

EpiCase AF: 0.290

EpiControl AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.021	D
Polyphen		0.98	D
Vest4		0.036
MPC		0.012
ClinPred		0.016	T
GERP RS		2.5
Varity_R		0.093
gMVP		0.090

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

Publications

LitVar

Other links and lift over

dbSNP: rs35262183; hg19: chr5-121488506; COSMIC: COSV56945671; COSMIC: COSV56945671;