rs397515549

chrX-21971900-T-AchrX-21971900-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004595.5(SMS):c.174T>A(p.Phe58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SMS NM_004595.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.41

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]

ACMG classification

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
SMS	NM_004595.5	c.174T>A	p.Phe58Leu	missense_variant	3/11	ENST00000404933.7
SMS	XM_005274582.3	c.72T>A	p.Phe24Leu	missense_variant	3/11
SMS	XM_011545568.3	c.72T>A	p.Phe24Leu	missense_variant	3/11
SMS	NM_001258423.2	c.170+4584T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMS	ENST00000404933.7	c.174T>A	p.Phe58Leu	missense_variant	3/11	1	NM_004595.5	P1
SMS	ENST00000457085.2	c.519T>A	p.Phe173Leu	missense_variant	3/6	5
SMS	ENST00000379404.5	c.170+4584T>A		intron_variant		3
SMS	ENST00000478094.1	n.218-607T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Syndromic X-linked intellectual disability Snyder type Other:1

not provided, no classification provided

literature only

GeneReviews

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.065	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.45
Sift	Benign	0.37	T
Sift4G	Benign	0.66	T
Polyphen		0.032	B
Vest4		0.54
MutPred		0.65		Loss of sheet (P = 0.007);
MVP		0.98
MPC		1.1
ClinPred		0.36	T
GERP RS		3.2
Varity_R		0.68
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.41		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397515549; hg19: chrX-21990018;