rs267607076
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_004595.5(SMS):c.395T>G(p.Val132Gly) 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. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Consequence
SMS
NM_004595.5 missense
NM_004595.5 missense
Scores
8
6
3
Clinical Significance
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 7 ACMG points.
PM1
?
In a domain PABS (size 240) in uniprot entity SPSY_HUMAN there are 15 pathogenic changes around while only 2 benign (88%) in NM_004595.5
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.904
PP5
?
Variant X-21977126-T-G is Pathogenic according to our data. Variant chrX-21977126-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 11625.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMS | NM_004595.5 | c.395T>G | p.Val132Gly | missense_variant | 5/11 | ENST00000404933.7 | |
SMS | NM_001258423.2 | c.236T>G | p.Val79Gly | missense_variant | 3/9 | ||
SMS | XM_005274582.3 | c.293T>G | p.Val98Gly | missense_variant | 5/11 | ||
SMS | XM_011545568.3 | c.293T>G | p.Val98Gly | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMS | ENST00000404933.7 | c.395T>G | p.Val132Gly | missense_variant | 5/11 | 1 | NM_004595.5 | P1 | |
SMS | ENST00000457085.2 | c.740T>G | p.Val247Gly | missense_variant | 5/6 | 5 | |||
SMS | ENST00000379404.5 | c.236T>G | p.Val79Gly | missense_variant | 3/9 | 3 | |||
SMS | ENST00000478094.1 | n.348T>G | non_coding_transcript_exon_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Syndromic X-linked intellectual disability Snyder type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
D;D
Vest4
MutPred
Loss of stability (P = 0.0236);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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