X-137565967-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_003413.4(ZIC3):​c.-725C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 111,641 control chromosomes in the GnomAD database, including 7,251 homozygotes. There are 14,114 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 7251 hom., 14114 hem., cov: 24)

Consequence

ZIC3
NM_003413.4 upstream_gene

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.172
Variant links:
Genes affected
ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant X-137565967-C-T is Benign according to our data. Variant chrX-137565967-C-T is described in ClinVar as [Benign]. Clinvar id is 1239042.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZIC3NM_003413.4 linkc.-725C>T upstream_gene_variant ENST00000287538.10 NP_003404.1
ZIC3NM_001330661.1 linkc.-725C>T upstream_gene_variant NP_001317590.1 O60481-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZIC3ENST00000287538.10 linkc.-725C>T upstream_gene_variant 1 NM_003413.4 ENSP00000287538.5 O60481-1

Frequencies

GnomAD3 genomes
AF:
0.413
AC:
46036
AN:
111600
Hom.:
7259
Cov.:
24
AF XY:
0.416
AC XY:
14111
AN XY:
33898
show subpopulations
Gnomad AFR
AF:
0.211
Gnomad AMI
AF:
0.493
Gnomad AMR
AF:
0.499
Gnomad ASJ
AF:
0.385
Gnomad EAS
AF:
0.395
Gnomad SAS
AF:
0.491
Gnomad FIN
AF:
0.487
Gnomad MID
AF:
0.377
Gnomad NFE
AF:
0.503
Gnomad OTH
AF:
0.415
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.412
AC:
46022
AN:
111641
Hom.:
7251
Cov.:
24
AF XY:
0.416
AC XY:
14114
AN XY:
33949
show subpopulations
Gnomad4 AFR
AF:
0.210
Gnomad4 AMR
AF:
0.498
Gnomad4 ASJ
AF:
0.385
Gnomad4 EAS
AF:
0.395
Gnomad4 SAS
AF:
0.492
Gnomad4 FIN
AF:
0.487
Gnomad4 NFE
AF:
0.503
Gnomad4 OTH
AF:
0.410
Alfa
AF:
0.460
Hom.:
3295
Bravo
AF:
0.400

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 17, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Benign
16
DANN
Uncertain
0.99

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12843772; hg19: chrX-136648126; API