Genetic Variant ZCCHC2:p.Pro23Ser (chr18-62523491-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017742.6(ZCCHC2):c.67C>T(p.Pro23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,013,102 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZCCHC2
NM_017742.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.537

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04111913).

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.67C>T	p.Pro23Ser	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.467C>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.67C>T	p.Pro23Ser	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
ZCCHC2	ENST00000963441.1		c.67C>T	p.Pro23Ser	missense	Exon 1 of 14	ENSP00000633500.1
ZCCHC2	ENST00000585873.5	TSL:1	n.-177C>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes

AF:

0.0000759

AC:

AN:

144844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000682

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:

0.000138

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000110

AC:

AN:

18172

AF XY:

0.0000825

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:

0.000257

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

AN:

868258

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

408720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16110

American (AMR)

AF:

0.00

AC:

AN:

2326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7482

East Asian (EAS)

AF:

0.00

AC:

AN:

4174

South Asian (SAS)

AF:

0.00

AC:

AN:

25222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1806

European-Non Finnish (NFE)

AF:

0.000120

AC:

AN:

780286

Other (OTH)

AF:

0.000105

AC:

AN:

28692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000759

AC:

AN:

144844

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

70366

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40360

American (AMR)

AF:

0.0000682

AC:

AN:

14670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

4904

South Asian (SAS)

AF:

0.00

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000138

AC:

AN:

65334

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.36

M_CAP

Benign

0.077

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.54

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.69

REVEL

Benign

0.0070

Sift

Benign

0.12

Sift4G

Benign

0.10

Polyphen

0.0060

Vest4

0.088

MutPred

0.16

Gain of phosphorylation at P23 (P = 9e-04)

MVP

0.014

MPC

0.042

ClinPred

0.030

GERP RS

1.1

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.046

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over