chrX-50602636-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020717.5(SHROOM4):c.3939A>T(p.Lys1313Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 111,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Consequence
SHROOM4
NM_020717.5 missense
NM_020717.5 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 2.37
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHROOM4 | NM_020717.5 | c.3939A>T | p.Lys1313Asn | missense_variant | 7/9 | ENST00000376020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHROOM4 | ENST00000376020.9 | c.3939A>T | p.Lys1313Asn | missense_variant | 7/9 | 2 | NM_020717.5 | P1 | |
SHROOM4 | ENST00000289292.11 | c.3939A>T | p.Lys1313Asn | missense_variant | 7/10 | 1 | P1 | ||
SHROOM4 | ENST00000460112.3 | c.3591A>T | p.Lys1197Asn | missense_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 111395Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33569
GnomAD3 genomes
?
AF:
AC:
2
AN:
111395
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
33569
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 Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 111395Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33569
GnomAD4 genome
?
AF:
AC:
2
AN:
111395
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
33569
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
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 | Ambry Genetics | Mar 14, 2023 | The c.3939A>T (p.K1313N) alteration is located in exon 7 (coding exon 7) of the SHROOM4 gene. This alteration results from a A to T substitution at nucleotide position 3939, causing the lysine (K) at amino acid position 1313 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;.
Vest4
MutPred
Loss of ubiquitination at K1313 (P = 0.0199);Loss of ubiquitination at K1313 (P = 0.0199);.;
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