rs1300131974

Variant names:

• chrX-21940869-C-A
• rs1300131974
• NM_004595.5:c.45C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-21940869-C-A
• chrX-21940869-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004595.5(SMS):​c.45C>A​(p.Ala15Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SMS NM_004595.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 0 publications found

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]

SMS Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Snyder type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.099 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004595.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	NM_004595.5	MANE Select	c.45C>A	p.Ala15Ala	synonymous	Exon 1 of 11	NP_004586.2
	SMS	NM_001258423.2		c.45C>A	p.Ala15Ala	synonymous	Exon 1 of 9	NP_001245352.1	P52788-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	ENST00000404933.7	TSL:1 MANE Select	c.45C>A	p.Ala15Ala	synonymous	Exon 1 of 11	ENSP00000385746.2	P52788-1
	SMS	ENST00000853889.1		c.45C>A	p.Ala15Ala	synonymous	Exon 1 of 12	ENSP00000523948.1
	SMS	ENST00000955899.1		c.45C>A	p.Ala15Ala	synonymous	Exon 1 of 12	ENSP00000625958.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00 AC: 0 AN: 65135 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 986190 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 313292

African (AFR) AF: 0.00 AC: 0 AN: 20707

American (AMR) AF: 0.00 AC: 0 AN: 23121

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16706

East Asian (EAS) AF: 0.00 AC: 0 AN: 21683

South Asian (SAS) AF: 0.00 AC: 0 AN: 45900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24741

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 789600

Other (OTH) AF: 0.00 AC: 0 AN: 41088

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		-0.099
PromoterAI		0.090	Neutral

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

Other links and lift over

dbSNP: rs1300131974; hg19: chrX-21958987;