Genetic Variant ZNF474:p.Pro63Leu (chr5-122152178-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207317.3(ZNF474):c.188C>T(p.Pro63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P63A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF474
NM_207317.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

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

ZNF474 links:

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

ENSG00000250803 links:

ENSG00000247311 (HGNC:):

ENSG00000247311 links:

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

ZNF474-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF474	NM_207317.3 link	c.188C>T	p.Pro63Leu	missense_variant	Exon 2 of 2	ENST00000296600.5	NP_997200.1	Q6S9Z5
ZNF474-AS1	XR_007058915.1 link	n.272-1575G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5 link	c.188C>T	p.Pro63Leu	missense_variant	Exon 2 of 2	1	NM_207317.3	ENSP00000296600.4		Q6S9Z5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.49

T;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

1.0

D;.

Vest4

0.52

MutPred

0.28

Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);

MVP

0.41

MPC

0.016

ClinPred

0.99

GERP RS

5.6

Varity_R

0.18

gMVP

0.070

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over