Genetic Variant ZCCHC2:p.Lys32* (chr18-62523518-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_017742.6(ZCCHC2):c.94A>T(p.Lys32*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZCCHC2
NM_017742.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

0 publications found

Variant links:

Genes affected

ZCCHC2 (HGNC:22916): (zinc finger CCHC-type containing 2) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017742.6. 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
	ZCCHC2	NM_017742.6	MANE Select	c.94A>T	p.Lys32*	stop_gained	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.494A>T		non_coding_transcript_exon	Exon 1 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZCCHC2	ENST00000269499.10	TSL:5 MANE Select	c.94A>T	p.Lys32*	stop_gained	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
ZCCHC2	ENST00000963441.1		c.94A>T	p.Lys32*	stop_gained	Exon 1 of 14	ENSP00000633500.1
ZCCHC2	ENST00000585873.5	TSL:1	n.-150A>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes

AF:

0.00000761

AC:

AN:

131492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000271

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;AS_VQSR

AF:

0.00

AC:

AN:

528202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

246336

African (AFR)

AF:

0.00

AC:

AN:

9998

American (AMR)

AF:

0.00

AC:

AN:

686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

2380

South Asian (SAS)

AF:

0.00

AC:

AN:

11018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1020

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

482244

Other (OTH)

AF:

0.00

AC:

AN:

17292

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000760

AC:

AN:

131526

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

63514

show subpopulations

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

African (AFR)

AF:

0.0000271

AC:

AN:

36932

American (AMR)

AF:

0.00

AC:

AN:

13694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3212

East Asian (EAS)

AF:

0.00

AC:

AN:

3740

South Asian (SAS)

AF:

0.00

AC:

AN:

3710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60982

Other (OTH)

AF:

0.00

AC:

AN:

1854

⚠️ 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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.034

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.030

PhyloP100

1.8

Vest4

0.095

GERP RS

0.21

PromoterAI

0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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