rs750900457

Variant names:

• chr5-122152177-C-A
• rs750900457
• NM_207317.3:c.187C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-122152177-C-A
• chr5-122152177-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207317.3(ZNF474):​c.187C>A​(p.Pro63Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P63A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.187C>A	p.Pro63Thr	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.187C>A	p.Pro63Thr	missense	Exon 2 of 2	ENSP00000296600.4	Q6S9Z5
	ZNF474	ENST00000698749.1		c.187C>A	p.Pro63Thr	missense	Exon 2 of 4	ENSP00000513911.1	A0A8V8TNM7
	ZNF474	ENST00000698748.1		c.187C>A	p.Pro63Thr	missense	Exon 2 of 6	ENSP00000513910.1	A0A8V8TM77

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250886 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 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: 0.00 AC: 0 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: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

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	0.26
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.1
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.26		Gain of sheet (P = 0.0266)
MVP		0.46
MPC		0.015
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.20
gMVP		0.090
Mutation Taster		=87/13	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: rs750900457; hg19: chr5-121487872;