X-21945025-A-G

Variant names:

• chrX-21945025-A-G
• rs2238958
• NM_004595.5:c.49+4152A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004595.5(SMS):​c.49+4152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (14841 hom., 18530 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 2 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), Orphanet, ClinGen, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	NM_004595.5	MANE Select	c.49+4152A>G		intron	N/A	NP_004586.2
	SMS	NM_001258423.2		c.49+4152A>G		intron	N/A	NP_001245352.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	ENST00000404933.7	TSL:1 MANE Select	c.49+4152A>G		intron	N/A	ENSP00000385746.2
	SMS	ENST00000457085.2	TSL:5	c.394+3658A>G		intron	N/A	ENSP00000407366.2
	SMS	ENST00000379404.5	TSL:3	c.49+4152A>G		intron	N/A	ENSP00000368714.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 63497 AN: 110114 Hom.: 14823 Cov.: 22

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.529

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.577 AC: 63572 AN: 110168 Hom.: 14841 Cov.: 22 AF XY: 0.571 AC XY: 18530 AN XY: 32462

African (AFR) AF: 0.901 AC: 27232 AN: 30235

American (AMR) AF: 0.602 AC: 6241 AN: 10363

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1010 AN: 2635

East Asian (EAS) AF: 0.497 AC: 1721 AN: 3466

South Asian (SAS) AF: 0.395 AC: 1040 AN: 2636

European-Finnish (FIN) AF: 0.501 AC: 2874 AN: 5740

Middle Eastern (MID) AF: 0.391 AC: 84 AN: 215

European-Non Finnish (NFE) AF: 0.423 AC: 22295 AN: 52703

Other (OTH) AF: 0.533 AC: 802 AN: 1505

Alfa AF: 0.504 Hom.: 51984

Bravo AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2238958; hg19: chrX-21963143;