rs149300669
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_020717.5(SHROOM4):c.3944T>C(p.Ile1315Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,201,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 268 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020717.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHROOM4 | NM_020717.5 | c.3944T>C | p.Ile1315Thr | missense_variant, splice_region_variant | 8/9 | ENST00000376020.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHROOM4 | ENST00000376020.9 | c.3944T>C | p.Ile1315Thr | missense_variant, splice_region_variant | 8/9 | 2 | NM_020717.5 | P1 | |
SHROOM4 | ENST00000289292.11 | c.3944T>C | p.Ile1315Thr | missense_variant, splice_region_variant | 8/10 | 1 | P1 | ||
SHROOM4 | ENST00000460112.3 | c.3596T>C | p.Ile1199Thr | missense_variant, splice_region_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000679 AC: 76AN: 111942Hom.: 0 Cov.: 22 AF XY: 0.000645 AC XY: 22AN XY: 34114
GnomAD3 exomes AF: 0.000465 AC: 76AN: 163482Hom.: 0 AF XY: 0.000445 AC XY: 23AN XY: 51636
GnomAD4 exome AF: 0.000655 AC: 714AN: 1089535Hom.: 0 Cov.: 31 AF XY: 0.000690 AC XY: 246AN XY: 356363
GnomAD4 genome AF: 0.000679 AC: 76AN: 111997Hom.: 0 Cov.: 22 AF XY: 0.000644 AC XY: 22AN XY: 34179
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 24, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | SHROOM4: BP4, BS2 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The c.3944T>C (p.I1315T) alteration is located in exon 8 (coding exon 8) of the SHROOM4 gene. This alteration results from a T to C substitution at nucleotide position 3944, causing the isoleucine (I) at amino acid position 1315 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
See cases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Feb 25, 2020 | ACMG classification criteria: BS2, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at