5-122152178-C-G

Variant names:

• chr5-122152178-C-G
• rs761268305
• NM_207317.3:c.188C>G

Variant summary

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

The NM_207317.3(ZNF474):​c.188C>G​(p.Pro63Arg) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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:):

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

ACMG classification

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	c.188C>G	p.Pro63Arg	missense_variant	Exon 2 of 2	ENST00000296600.5	NP_997200.1
ZNF474-AS1	XR_007058915.1	n.272-1575G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF474	ENST00000296600.5	c.188C>G	p.Pro63Arg	missense_variant	Exon 2 of 2	1	NM_207317.3	ENSP00000296600.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250866 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135662

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.098	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;.
Vest4		0.57
MutPred		0.26		Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);
MVP		0.47
MPC		0.016
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.058

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

LitVar

Other links and lift over

dbSNP: rs761268305; hg19: chr5-121487873;