rs776474446
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBP6_Very_Strong
The NM_015001.3(SPEN):āc.9730A>Cā(p.Thr3244Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3244A) has been classified as Likely benign.
Frequency
Consequence
NM_015001.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPEN | NM_015001.3 | c.9730A>C | p.Thr3244Pro | missense_variant | 11/15 | ENST00000375759.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPEN | ENST00000375759.8 | c.9730A>C | p.Thr3244Pro | missense_variant | 11/15 | 1 | NM_015001.3 | P1 | |
SPEN | ENST00000704274.1 | c.5329A>C | p.Thr1777Pro | missense_variant | 1/4 | ||||
SPEN | ENST00000438066.2 | c.*10581A>C | 3_prime_UTR_variant, NMD_transcript_variant | 11/15 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 11775AN: 52116Hom.: 0 Cov.: 9 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.121 AC: 58030AN: 480860Hom.: 0 Cov.: 35 AF XY: 0.109 AC XY: 27060AN XY: 248002
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.226 AC: 11773AN: 52112Hom.: 0 Cov.: 9 AF XY: 0.219 AC XY: 5411AN XY: 24762
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Fails ExAC quality filter - |
SPEN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at