X-21967231-A-G

Position:

• chrX-21967231-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004595.5(SMS):​c.85A>G​(p.Ile29Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: SMS NM_004595.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117243916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5	c.85A>G	p.Ile29Val	missense_variant	2/11	ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.85A>G	p.Ile29Val	missense_variant	2/9		NP_001245352.1
SMS	XM_005274582.3	c.-18A>G		5_prime_UTR_variant	2/11		XP_005274639.1
SMS	XM_011545568.3	c.-18A>G		5_prime_UTR_variant	2/11		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.85A>G	p.Ile29Val	missense_variant	2/11	1	NM_004595.5	ENSP00000385746	P1
SMS	ENST00000457085.2	c.430A>G	p.Ile144Val	missense_variant	2/6	5		ENSP00000407366
SMS	ENST00000379404.5	c.85A>G	p.Ile29Val	missense_variant	2/9	3		ENSP00000368714
SMS	ENST00000478094.1	n.132A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.24
Sift	Benign	0.41	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.28		Loss of methylation at K24 (P = 0.0884);Loss of methylation at K24 (P = 0.0884);
MVP		0.65
MPC		0.75
ClinPred		0.71	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-21985349;