chr19-50041811-C-A

Variant names:

• chr19-50041811-C-A
• rs944080625
• NM_015428.4:c.218C>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.218C>A​(p.Thr73Lys) 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. 16/22 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. T73I) 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: -2.10
• 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]

ENSG00000298681 (HGNC:):

ZNF473-AS1 (HGNC:58330):

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=0.08943343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF473	NM_015428.4	c.218C>A	p.Thr73Lys	missense_variant	Exon 4 of 5	ENST00000270617.8	NP_056243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF473	ENST00000270617.8	c.218C>A	p.Thr73Lys	missense_variant	Exon 4 of 5	1	NM_015428.4	ENSP00000270617.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.012
DANN	Benign	0.18
DEOGEN2	Benign	0.0029	.;T;T;T;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.26	T;.;.;T;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.089	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	.;L;L;L;.;.;.
PhyloP100		-2.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	.;.;N;N;N;.;.
REVEL	Benign	0.0080
Sift	Benign	0.14	.;.;T;T;T;.;.
Sift4G	Pathogenic	0.0	D;T;T;T;T;D;D
Polyphen		0.0040	.;B;B;B;.;.;.
Vest4		0.10, 0.075, 0.093, 0.10
MutPred		0.30		Gain of ubiquitination at T73 (P = 0.0039);Gain of ubiquitination at T73 (P = 0.0039);Gain of ubiquitination at T73 (P = 0.0039);Gain of ubiquitination at T73 (P = 0.0039);.;Gain of ubiquitination at T73 (P = 0.0039);Gain of ubiquitination at T73 (P = 0.0039);
MVP		0.21
MPC		0.34
ClinPred		0.38	T
GERP RS		-7.7
Varity_R		0.042
gMVP		0.19
Mutation Taster		=98/2	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: rs944080625; hg19: chr19-50545068;