chr5-122152264-C-T

Variant names:

• chr5-122152264-C-T
• rs1580611662
• NM_207317.3:c.274C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_207317.3(ZNF474):​c.274C>T​(p.Pro92Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.274C>T	p.Pro92Ser	missense	Exon 2 of 2	NP_997200.1	Q6S9Z5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF474	ENST00000296600.5	TSL:1 MANE Select	c.274C>T	p.Pro92Ser	missense	Exon 2 of 2	ENSP00000296600.4	Q6S9Z5
	ZNF474	ENST00000698749.1		c.274C>T	p.Pro92Ser	missense	Exon 2 of 4	ENSP00000513911.1	A0A8V8TNM7
	ZNF474	ENST00000698748.1		c.274C>T	p.Pro92Ser	missense	Exon 2 of 6	ENSP00000513910.1	A0A8V8TM77

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.8
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.68		Gain of phosphorylation at P92 (P = 0.0208)
MVP		0.75
MPC		0.013
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.52
gMVP		0.091
Mutation Taster		=86/14	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: rs1580611662; hg19: chr5-121487959;