rs397515552
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_004595.5(SMS):āc.449T>Cā(p.Ile150Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 23)
Exomes š: 9.1e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
SMS
NM_004595.5 missense
NM_004595.5 missense
Scores
10
5
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.64
Genes affected
SMS (HGNC:11123): (spermine synthase) This gene encodes a protein belonging to the spermidine/spermin synthase family and catalyzes the production of spermine from spermidine. Pseudogenes of this gene are located on chromosomes 1, 5, 6 and X. Mutations in this gene cause an X-linked intellectual disability called Snyder-Robinson Syndrome (SRS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMS | NM_004595.5 | c.449T>C | p.Ile150Thr | missense_variant | 5/11 | ENST00000404933.7 | NP_004586.2 | |
SMS | NM_001258423.2 | c.290T>C | p.Ile97Thr | missense_variant | 3/9 | NP_001245352.1 | ||
SMS | XM_005274582.3 | c.347T>C | p.Ile116Thr | missense_variant | 5/11 | XP_005274639.1 | ||
SMS | XM_011545568.3 | c.347T>C | p.Ile116Thr | missense_variant | 5/11 | XP_011543870.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMS | ENST00000404933.7 | c.449T>C | p.Ile150Thr | missense_variant | 5/11 | 1 | NM_004595.5 | ENSP00000385746 | P1 | |
SMS | ENST00000457085.2 | c.794T>C | p.Ile265Thr | missense_variant | 5/6 | 5 | ENSP00000407366 | |||
SMS | ENST00000379404.5 | c.290T>C | p.Ile97Thr | missense_variant | 3/9 | 3 | ENSP00000368714 | |||
SMS | ENST00000478094.1 | n.402T>C | non_coding_transcript_exon_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.14e-7 AC: 1AN: 1093941Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 359375
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1093941
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
359375
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 Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;P
Vest4
MutPred
Loss of stability (P = 0.0103);.;
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