Genetic Variant ZC3H7B:p.Leu221Leu (chr22-41339038-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_017590.6(ZC3H7B):c.663C>T(p.Leu221Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZC3H7B
NM_017590.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.730

Publications

1 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 -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 22-41339038-C-T is Benign according to our data. Variant chr22-41339038-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3472636.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.73 with no splicing effect.

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.663C>T	p.Leu221Leu	synonymous	Exon 9 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.663C>T	p.Leu221Leu	synonymous	Exon 9 of 23	ENSP00000345793.4	Q9UGR2
ZC3H7B	ENST00000926343.1		c.563C>T	p.Ser188Phe	missense	Exon 7 of 21	ENSP00000596402.1
ZC3H7B	ENST00000897616.1		c.663C>T	p.Leu221Leu	synonymous	Exon 9 of 23	ENSP00000567675.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722100

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.00

AC:

AN:

84942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107194

Other (OTH)

AF:

0.00

AC:

AN:

60088

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.5

(source)

DANN

Benign

0.65

PhyloP100

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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

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