Genetic Variant ZCCHC13:p.Thr93Asn (chrX-74304544-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_203303.3(ZCCHC13):c.278C>A(p.Thr93Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,210,939 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 9 hem. )

Consequence

ZCCHC13
NM_203303.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.310

Publications

0 publications found

Variant links:

Genes affected

ZCCHC13 (HGNC:31749): (zinc finger CCHC-type containing 13) This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 3. However, the CDS of this intronless gene remains relatively intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein. The encoded protein contains six CCHC-type zinc fingers, and is thus thought to function as a transcription factor. [provided by RefSeq, May 2010]

ZCCHC13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13335261).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203303.3. 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
	ZCCHC13	NM_203303.3	MANE Select	c.278C>A	p.Thr93Asn	missense	Exon 1 of 1	NP_976048.1	Q8WW36

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC13	ENST00000339534.4	TSL:6 MANE Select	c.278C>A	p.Thr93Asn	missense	Exon 1 of 1	ENSP00000345633.2	Q8WW36

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112693

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183389

AF XY:

0.0000442

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:

0.0000489

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1098246

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

842132

Other (OTH)

AF:

0.00

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00000887

AC:

AN:

112693

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34831

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31049

American (AMR)

AF:

0.00

AC:

AN:

10691

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3589

South Asian (SAS)

AF:

0.00

AC:

AN:

2749

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6193

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53332

Other (OTH)

AF:

0.00

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.000132

Hom.:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

0.094

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0060

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0012

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0029

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

0.31

PrimateAI

Benign

0.34

PROVEAN

Benign

0.37

REVEL

Benign

0.029

Sift

Benign

0.70

Sift4G

Benign

0.78

Polyphen

0.0020

Vest4

0.20

MVP

0.055

MPC

0.44

ClinPred

0.015

GERP RS

-3.4

PromoterAI

0.044

Neutral

(source)

Varity_R

0.051

gMVP

0.30

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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