Genetic Variant NM_017742.6:c.191C>T (chr18-62523615-C-T) – 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_017742.6(ZCCHC2):c.191C>T(p.Pro64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 146,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZCCHC2
NM_017742.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041426033).

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.191C>T	p.Pro64Leu	missense	Exon 1 of 14	NP_060212.4
	ZCCHC2	NR_126534.2		n.591C>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.191C>T	p.Pro64Leu	missense	Exon 1 of 14	ENSP00000269499.4	Q9C0B9-1
ZCCHC2	ENST00000963441.1		c.191C>T	p.Pro64Leu	missense	Exon 1 of 14	ENSP00000633500.1
ZCCHC2	ENST00000585873.5	TSL:1	n.-53C>T		upstream_gene	N/A	ENSP00000468789.1	K7ESN2

Frequencies

GnomAD3 genomes

AF:

0.00000681

AC:

AN:

146748

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:

0.00

Gnomad SAS

AF:

0.000208

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:

1033904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

487682

African (AFR)

AF:

0.00

AC:

AN:

21160

American (AMR)

AF:

0.00

AC:

AN:

6794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12262

East Asian (EAS)

AF:

0.00

AC:

AN:

22714

South Asian (SAS)

AF:

0.00

AC:

AN:

18870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

890612

Other (OTH)

AF:

0.00

AC:

AN:

40174

GnomAD4 genome

AF:

0.00000681

AC:

AN:

146748

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40754

American (AMR)

AF:

0.00

AC:

AN:

14816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

5034

South Asian (SAS)

AF:

0.000208

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65970

Other (OTH)

AF:

0.00

AC:

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

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

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.54

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.90

REVEL

Benign

0.055

Sift

Benign

0.23

Sift4G

Uncertain

0.028

Polyphen

0.0

Vest4

0.17

MutPred

0.18

Loss of relative solvent accessibility (P = 0.008)

MVP

0.014

MPC

0.043

ClinPred

0.11

GERP RS

1.7

PromoterAI

0.00040

Neutral

(source)

Varity_R

0.040

gMVP

0.24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over