rs144727288
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_020717.5(SHROOM4):āc.2192A>Gā(p.Glu731Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,210,477 control chromosomes in the GnomAD database, including 6 homozygotes. There are 883 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0022 ( 6 hom., 74 hem., cov: 23)
Exomes š: 0.0023 ( 0 hom. 809 hem. )
Consequence
SHROOM4
NM_020717.5 missense
NM_020717.5 missense
Scores
4
6
7
Clinical Significance
Conservation
PhyloP100: 2.12
Genes affected
SHROOM4 (HGNC:29215): (shroom family member 4) This gene encodes a member of the APX/Shroom family, which contain an N-terminal PDZ domain and a C-terminal ASD2 motif. The encoded protein may play a role in cytoskeletal architecture. Mutations in this gene have been linked to the X-linked Stocco dos Santos syndrome characterized by cognitive disabilities. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.013019592).
BP6
Variant X-50633881-T-C is Benign according to our data. Variant chrX-50633881-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 197325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-50633881-T-C is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SHROOM4 | NM_020717.5 | c.2192A>G | p.Glu731Gly | missense_variant | 4/9 | ENST00000376020.9 | NP_065768.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHROOM4 | ENST00000376020.9 | c.2192A>G | p.Glu731Gly | missense_variant | 4/9 | 2 | NM_020717.5 | ENSP00000365188 | P1 | |
SHROOM4 | ENST00000289292.11 | c.2192A>G | p.Glu731Gly | missense_variant | 4/10 | 1 | ENSP00000289292 | P1 | ||
SHROOM4 | ENST00000460112.3 | c.1844A>G | p.Glu615Gly | missense_variant | 3/8 | 5 | ENSP00000421450 |
Frequencies
GnomAD3 genomes AF: 0.00218 AC: 245AN: 112316Hom.: 6 Cov.: 23 AF XY: 0.00215 AC XY: 74AN XY: 34480
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GnomAD3 exomes AF: 0.00136 AC: 249AN: 183079Hom.: 0 AF XY: 0.00130 AC XY: 88AN XY: 67567
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GnomAD4 exome AF: 0.00227 AC: 2490AN: 1098161Hom.: 0 Cov.: 33 AF XY: 0.00223 AC XY: 809AN XY: 363515
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GnomAD4 genome AF: 0.00218 AC: 245AN: 112316Hom.: 6 Cov.: 23 AF XY: 0.00215 AC XY: 74AN XY: 34480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 22, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 13, 2019 | Has not been previously published as pathogenic or benign to our knowledge - |
X-linked intellectual disability, Stocco dos Santos type Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;T
Polyphen
D;D;.
Vest4
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