chr19-50045149-C-A

Variant names:

• chr19-50045149-C-A
• rs1435223842
• NM_015428.4:c.706C>A

Variant summary

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

The NM_015428.4(ZNF473):​c.706C>A​(p.Pro236Thr) 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. P236A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF473 NM_015428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 0 publications found

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

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=0.19776112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF473	NM_015428.4	c.706C>A	p.Pro236Thr	missense_variant	Exon 5 of 5	ENST00000270617.8	NP_056243.1
ZNF473	NM_001006656.4	c.706C>A	p.Pro236Thr	missense_variant	Exon 5 of 5		NP_001006657.1
ZNF473	NM_001308424.3	c.670C>A	p.Pro224Thr	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.706C>A	p.Pro236Thr	missense_variant	Exon 5 of 5	1	NM_015428.4	ENSP00000270617.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.85	.;.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PhyloP100		0.80
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.5	.;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.072	.;T;T;T
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.99	D;D;D;.
Vest4		0.097
MutPred		0.40		Gain of phosphorylation at P236 (P = 0.0522);Gain of phosphorylation at P236 (P = 0.0522);Gain of phosphorylation at P236 (P = 0.0522);.;
MVP		0.56
MPC		0.96
ClinPred		0.93	D
GERP RS		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.091
Mutation Taster		=74/26	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: rs1435223842; hg19: chr19-50548406;