rs35262183

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-122152811-C-A
• chr5-122152811-C-G

Variant summary

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

The NM_207317.3(ZNF474):​c.821C>A​(p.Ser274Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 0 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: 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=0.06545207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF474	NM_207317.3	c.821C>A	p.Ser274Tyr	missense_variant	Exon 2 of 2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1	n.271+1813G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5	c.821C>A	p.Ser274Tyr	missense_variant	Exon 2 of 2	1	NM_207317.3	ENSP00000296600.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.5
DANN	Benign	0.59
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.077
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.016	D
Polyphen		0.0060	B
Vest4		0.15
MutPred		0.28		Gain of catalytic residue at S274 (P = 0.0103);
MVP		0.23
MPC		0.0035
ClinPred		0.063	T
GERP RS		2.5
Varity_R		0.053
gMVP		0.087
Mutation Taster		=100/0	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: rs35262183; hg19: chr5-121488506;