chrX-137566796-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003413.4(ZIC3):c.105G>A(p.Met35Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000272 in 1,176,305 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 25)
Exomes 𝑓: 0.000029 ( 0 hom. 14 hem. )
Consequence
ZIC3
NM_003413.4 missense
NM_003413.4 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 4.62
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 Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.100815475).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZIC3 | NM_003413.4 | c.105G>A | p.Met35Ile | missense_variant | 1/3 | ENST00000287538.10 | |
ZIC3 | NM_001330661.1 | c.105G>A | p.Met35Ile | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZIC3 | ENST00000287538.10 | c.105G>A | p.Met35Ile | missense_variant | 1/3 | 1 | NM_003413.4 | P1 | |
ZIC3 | ENST00000370606.3 | c.105G>A | p.Met35Ile | missense_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000884 AC: 1AN: 113101Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35247
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GnomAD4 exome AF: 0.0000292 AC: 31AN: 1063204Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 14AN XY: 345270
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GnomAD4 genome ? AF: 0.00000884 AC: 1AN: 113101Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35247
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Heterotaxy, visceral, 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 21, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at