Genetic Variant ZCCHC2:p.Pro57Leu (chr18-62523594-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.170C>T(p.Pro57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,027,728 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 0.000091 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ZCCHC2
NM_017742.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

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=0.030849785).

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.170C>T	p.Pro57Leu	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.570C>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.170C>T	p.Pro57Leu	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
ZCCHC2	ENST00000963441.1		c.170C>T	p.Pro57Leu	missense	Exon 1 of 14	ENSP00000633500.1
ZCCHC2	ENST00000585873.5	TSL:1	n.-74C>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes

AF:

0.0000914

AC:

AN:

142254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00259

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000508

GnomAD4 exome

AF:

0.0000260

AC:

AN:

885426

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

413356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17228

American (AMR)

AF:

0.00

AC:

AN:

2984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7308

East Asian (EAS)

AF:

0.00137

AC:

AN:

9484

South Asian (SAS)

AF:

0.00

AC:

AN:

16974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2006

European-Non Finnish (NFE)

AF:

0.00000252

AC:

AN:

792106

Other (OTH)

AF:

0.000259

AC:

AN:

30928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000914

AC:

AN:

142302

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

69126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39800

American (AMR)

AF:

0.00

AC:

AN:

14470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3360

East Asian (EAS)

AF:

0.00260

AC:

AN:

4616

South Asian (SAS)

AF:

0.00

AC:

AN:

4530

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64350

Other (OTH)

AF:

0.000503

AC:

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

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:

0.00

Hom.:

Bravo

AF:

0.000117

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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.36

M_CAP

Benign

0.037

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.21

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.58

REVEL

Benign

0.066

Sift

Benign

1.0

Sift4G

Uncertain

0.042

Polyphen

0.90

Vest4

0.11

MutPred

0.21

Gain of catalytic residue at P57 (P = 0.0159)

MVP

0.076

MPC

0.043

ClinPred

0.17

GERP RS

2.1

PromoterAI

0.078

Neutral

(source)

Varity_R

0.028

gMVP

0.22

Mutation Taster

=91/9

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