Genetic Variant NM_017590.6:c.23C>A (chr22-41320683-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017590.6(ZC3H7B):c.23C>A(p.Ala8Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A8V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZC3H7B
NM_017590.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.40

Publications

0 publications found

Variant links:

Genes affected

ZC3H7B (HGNC:30869): (zinc finger CCCH-type containing 7B) This gene encodes a protein that contains a tetratricopeptide repeat domain. The encoded protein also interacts with the rotavirus non-structural protein NSP3. [provided by RefSeq, Jul 2008]

ZC3H7B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02989614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017590.6. 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
	ZC3H7B	NM_017590.6	MANE Select	c.23C>A	p.Ala8Glu	missense	Exon 2 of 23	NP_060060.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3H7B	ENST00000352645.5	TSL:1 MANE Select	c.23C>A	p.Ala8Glu	missense	Exon 2 of 23	ENSP00000345793.4	Q9UGR2
ZC3H7B	ENST00000897616.1		c.23C>A	p.Ala8Glu	missense	Exon 2 of 23	ENSP00000567675.1
ZC3H7B	ENST00000897617.1		c.23C>A	p.Ala8Glu	missense	Exon 2 of 22	ENSP00000567676.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251458

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455202

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25918

East Asian (EAS)

AF:

0.00

AC:

AN:

39326

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107872

Other (OTH)

AF:

0.00

AC:

AN:

59900

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.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.014

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.087

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

M_CAP

Benign

0.0064

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

PhyloP100

5.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

2.1

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.37

Loss of MoRF binding (P = 0.0061)

MVP

0.043

MPC

0.82

ClinPred

0.31

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.15

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over