19-50045314-C-G

Variant names:

• chr19-50045314-C-G
• rs150817871
• NM_015428.4:c.871C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015428.4(ZNF473):​c.871C>G​(p.Pro291Ala) 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 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P291S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF473 NM_015428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

Genes affected

ZNF473 (HGNC:23239): (zinc finger protein 473) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein, a component of the U7 snRNP complex, plays a role in histone 3'-end pre-mRNA processing and may be required for cell cycle progression to S phase. Expression level and methylation status of this gene may be correlated with bone mineral density. [provided by RefSeq, Jul 2016]

ENSG00000269091 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09403846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF473	NM_015428.4	c.871C>G	p.Pro291Ala	missense_variant	Exon 5 of 5	ENST00000270617.8	NP_056243.1
ZNF473	NM_001006656.4	c.871C>G	p.Pro291Ala	missense_variant	Exon 5 of 5		NP_001006657.1
ZNF473	NM_001308424.3	c.835C>G	p.Pro279Ala	missense_variant	Exon 4 of 4		NP_001295353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF473	ENST00000270617.8	c.871C>G	p.Pro291Ala	missense_variant	Exon 5 of 5	1	NM_015428.4	ENSP00000270617.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.0
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T;T;T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.69	.;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.0	.;D;D;D
REVEL	Benign	0.11
Sift	Benign	0.21	.;T;T;T
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.0010	B;B;B;.
Vest4		0.069
MutPred		0.49		Loss of catalytic residue at P291 (P = 0.0269);Loss of catalytic residue at P291 (P = 0.0269);Loss of catalytic residue at P291 (P = 0.0269);.;
MVP		0.42
MPC		0.80
ClinPred		0.20	T
GERP RS		0.57
Varity_R		0.084
gMVP		0.051

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: rs150817871; hg19: chr19-50548571;