chr19-50039238-C-G

Variant names:

• chr19-50039238-C-G
• NM_015428.4:c.87C>G

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.87C>G​(p.Asp29Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF473 NM_015428.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.333
• 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]

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=0.08797762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF473	NM_015428.4	c.87C>G	p.Asp29Glu	missense_variant	Exon 3 of 5	ENST00000270617.8	NP_056243.1
ZNF473	NM_001006656.4	c.87C>G	p.Asp29Glu	missense_variant	Exon 3 of 5		NP_001006657.1
ZNF473	NM_001308424.3	c.51C>G	p.Asp17Glu	missense_variant	Exon 2 of 4		NP_001295353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF473	ENST00000270617.8	c.87C>G	p.Asp29Glu	missense_variant	Exon 3 of 5	1	NM_015428.4	ENSP00000270617.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.87C>G (p.D29E) alteration is located in exon 3 (coding exon 2) of the ZNF473 gene. This alteration results from a C to G substitution at nucleotide position 87, causing the aspartic acid (D) at amino acid position 29 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.0010	.;T;T;T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.67	T;.;.;T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.088	T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.99	.;L;L;L;.;.;.
PhyloP100		0.33
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	.;.;N;N;N;.;.
REVEL	Benign	0.028
Sift	Benign	0.031	.;.;D;D;D;.;.
Sift4G	Uncertain	0.045	D;T;T;T;T;D;T
Polyphen		0.21	.;B;B;B;.;.;.
Vest4		0.42, 0.38, 0.38, 0.41, 0.10
MutPred		0.51		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.26
MPC		0.88
ClinPred		0.13	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.053
gMVP		0.088
Mutation Taster		=99/1	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

hg19: chr19-50542495;