Genetic Variant ZNF473:p.Glu79Asp (chr19-50044680-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015428.4(ZNF473):c.237G>T(p.Glu79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF473
NM_015428.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.609

Publications

0 publications found

Variant links:

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]

ZNF473 links:

ENSG00000269091 (HGNC:):

ENSG00000269091 links:

ZNF473-AS1 (HGNC:58330):

ZNF473-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.18980196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF473	NM_015428.4 link	c.237G>T	p.Glu79Asp	missense_variant	Exon 5 of 5	ENST00000270617.8	NP_056243.1	Q8WTR7A0A024QZI1
ZNF473	NM_001006656.4 link	c.237G>T	p.Glu79Asp	missense_variant	Exon 5 of 5		NP_001006657.1	Q8WTR7A0A024QZI1
ZNF473	NM_001308424.3 link	c.201G>T	p.Glu67Asp	missense_variant	Exon 4 of 4		NP_001295353.1	Q8WTR7F8WEC7B4DY71
ZNF473-AS1	XR_007067295.1 link	n.10C>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF473	ENST00000270617.8 link	c.237G>T	p.Glu79Asp	missense_variant	Exon 5 of 5	1	NM_015428.4	ENSP00000270617.3		Q8WTR7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456844

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33170

American (AMR)

AF:

0.00

AC:

AN:

44002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25732

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

85776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109576

Other (OTH)

AF:

0.0000166

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0024

T;T;T;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.53

.;.;T;T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

L;L;L;.;.

PhyloP100

0.61

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

.;N;N;N;.

REVEL

Benign

0.092

Sift

Benign

0.13

.;T;T;T;.

Sift4G

Benign

0.27

T;T;T;T;D

Polyphen

0.98

D;D;D;.;.

Vest4

0.10

MutPred

0.17

Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);.;Loss of loop (P = 0.0986);

MVP

0.44

MPC

0.64

ClinPred

0.82

GERP RS

-0.46

Varity_R

0.073

gMVP

0.095

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

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19-50044680-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over