5-122152177-C-G

Position:

• chr5-122152177-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207317.3(ZNF474):​c.187C>G​(p.Pro63Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3934632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF474	NM_207317.3	c.187C>G	p.Pro63Ala	missense_variant	2/2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1	n.272-1574G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5	c.187C>G	p.Pro63Ala	missense_variant	2/2	1	NM_207317.3	ENSP00000296600.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.187C>G (p.P63A) alteration is located in exon 2 (coding exon 1) of the ZNF474 gene. This alteration results from a C to G substitution at nucleotide position 187, causing the proline (P) at amino acid position 63 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.19
Sift	Benign	0.049	D;D
Sift4G	Benign	0.079	T;D
Polyphen		0.99	D;.
Vest4		0.37
MutPred		0.29		Loss of glycosylation at P63 (P = 0.0367);Loss of glycosylation at P63 (P = 0.0367);
MVP		0.41
MPC		0.016
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.040

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.

Other links and lift over

hg19: chr5-121487872;