chr5-122152057-C-G

Variant names:

• chr5-122152057-C-G
• rs529368378
• NM_207317.3:c.67C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207317.3(ZNF474):​c.67C>G​(p.Pro23Ala) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P23S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF474 NM_207317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07671332).

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.67C>G	p.Pro23Ala	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.67C>G	p.Pro23Ala	missense	Exon 2 of 2	ENSP00000296600.4	Q6S9Z5
	ZNF474	ENST00000698749.1		c.67C>G	p.Pro23Ala	missense	Exon 2 of 4	ENSP00000513911.1	A0A8V8TNM7
	ZNF474	ENST00000698748.1		c.67C>G	p.Pro23Ala	missense	Exon 2 of 6	ENSP00000513910.1	A0A8V8TM77

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251200 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.78
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.43
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.061
Sift	Uncertain	0.026	D
Sift4G	Benign	0.12	T
Polyphen		0.69	P
Vest4		0.16
MutPred		0.26		Gain of helix (P = 0.0022)
MVP		0.56
MPC		0.0075
ClinPred		0.22	T
GERP RS		3.9
Varity_R		0.064
gMVP		0.025
Mutation Taster		=94/6	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: rs529368378; hg19: chr5-121487752;