dbSNP rs371218809: ZCCHC13:p.Lys4GlyfsTer17 (chrX-74304275-TAA-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_203303.3(ZCCHC13):c.10_11delAA(p.Lys4GlyfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.000278 in 1,198,492 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 90 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 46 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 44 hem. )

Consequence

ZCCHC13
NM_203303.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.05

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-74304275-TAA-T is Benign according to our data. Variant chrX-74304275-TAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3050854.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 46 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.10_11delAA	p.Lys4GlyfsTer17	frameshift	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.10_11delAA	p.Lys4GlyfsTer17	frameshift	Exon 1 of 1	ENSP00000345633.2	Q8WW36

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

174

AN:

112469

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000562

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:

0.00263

GnomAD2 exomes

AF:

0.000402

AC:

AN:

159170

AF XY:

0.000253

show subpopulations

Gnomad AFR exome

AF:

0.00491

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000249

GnomAD4 exome

AF:

0.000145

AC:

158

AN:

1085970

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

353700

show subpopulations

African (AFR)

AF:

0.00530

AC:

139

AN:

26233

American (AMR)

AF:

0.000206

AC:

AN:

34062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18899

East Asian (EAS)

AF:

0.00

AC:

AN:

29908

South Asian (SAS)

AF:

0.00

AC:

AN:

52328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39906

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834959

Other (OTH)

AF:

0.000241

AC:

AN:

45591

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.00156

AC:

175

AN:

112522

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

34704

show subpopulations

African (AFR)

AF:

0.00532

AC:

165

AN:

31031

American (AMR)

AF:

0.000561

AC:

AN:

10696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3542

South Asian (SAS)

AF:

0.00

AC:

AN:

2719

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53233

Other (OTH)

AF:

0.00259

AC:

AN:

1542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.00161

Asia WGS

AF:

0.000398

AC:

AN:

2522

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ZCCHC13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.0

Mutation Taster

=158/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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