19-50041738-A-G

Variant names:

• chr19-50041738-A-G
• rs1978783490
• NM_015428.4:c.145A>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.145A>G​(p.Arg49Gly) 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. 15/22 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: 1.15
• 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=0.08590919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015428.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF473	NM_015428.4	MANE Select	c.145A>G	p.Arg49Gly	missense	Exon 4 of 5	NP_056243.1	Q8WTR7
	ZNF473	NM_001006656.4		c.145A>G	p.Arg49Gly	missense	Exon 4 of 5	NP_001006657.1	Q8WTR7
	ZNF473	NM_001308424.3		c.109A>G	p.Arg37Gly	missense	Exon 3 of 4	NP_001295353.1	F8WEC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF473	ENST00000270617.8	TSL:1 MANE Select	c.145A>G	p.Arg49Gly	missense	Exon 4 of 5	ENSP00000270617.3	Q8WTR7
	ZNF473	ENST00000391821.6	TSL:1	c.145A>G	p.Arg49Gly	missense	Exon 4 of 5	ENSP00000375697.1	Q8WTR7
	ZNF473	ENST00000595661.5	TSL:5	c.145A>G	p.Arg49Gly	missense	Exon 5 of 6	ENSP00000472808.1	Q8WTR7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.2
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.023
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.054	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.33		Gain of glycosylation at P50 (P = 0.1227)
MVP		0.15
MPC		0.38
ClinPred		0.11	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.14
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1978783490; hg19: chr19-50544995;