rs797045961
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_020717.5(SHROOM4):c.245G>A(p.Arg82Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,210,099 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts 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: 0.000010 ( 0 hom. 4 hem. )
Consequence
SHROOM4
NM_020717.5 missense
NM_020717.5 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 3.02
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21963626).
BS2
?
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHROOM4 | NM_020717.5 | c.245G>A | p.Arg82Gln | missense_variant | 2/9 | ENST00000376020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHROOM4 | ENST00000376020.9 | c.245G>A | p.Arg82Gln | missense_variant | 2/9 | 2 | NM_020717.5 | P1 | |
SHROOM4 | ENST00000289292.11 | c.245G>A | p.Arg82Gln | missense_variant | 2/10 | 1 | P1 | ||
SHROOM4 | ENST00000484922.1 | n.128G>A | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000893 AC: 1AN: 112009Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34181
GnomAD3 genomes
?
AF:
AC:
1
AN:
112009
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
34181
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000100 AC: 11AN: 1098090Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363468
GnomAD4 exome
AF:
AC:
11
AN:
1098090
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
363468
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000893 AC: 1AN: 112009Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34181
GnomAD4 genome
?
AF:
AC:
1
AN:
112009
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
34181
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 11, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of solvent accessibility (P = 0.0219);Loss of solvent accessibility (P = 0.0219);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at