X-21967846-C-T

Variant names:

• chrX-21967846-C-T
• rs732946
• NM_004595.5:c.170+530C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004595.5(SMS):​c.170+530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 111,970 control chromosomes in the GnomAD database, including 2,391 homozygotes. There are 5,127 hemizygotes in GnomAD. 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 0.16 (2391 hom., 5127 hem., cov: 23)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

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.170+530C>T		intron	N/A	NP_004586.2
	SMS	NM_001258423.2		c.170+530C>T		intron	N/A	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.170+530C>T		intron	N/A	ENSP00000385746.2	P52788-1
	SMS	ENST00000853889.1		c.170+530C>T		intron	N/A	ENSP00000523948.1
	SMS	ENST00000955899.1		c.170+530C>T		intron	N/A	ENSP00000625958.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 18221 AN: 111919 Hom.: 2386 Cov.: 23

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.00296

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00951

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.163 AC: 18251 AN: 111970 Hom.: 2391 Cov.: 23 AF XY: 0.150 AC XY: 5127 AN XY: 34154

African (AFR) AF: 0.449 AC: 13773 AN: 30675

American (AMR) AF: 0.0854 AC: 912 AN: 10677

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 305 AN: 2655

East Asian (EAS) AF: 0.00954 AC: 34 AN: 3564

South Asian (SAS) AF: 0.0907 AC: 246 AN: 2713

European-Finnish (FIN) AF: 0.0472 AC: 288 AN: 6103

Middle Eastern (MID) AF: 0.106 AC: 23 AN: 218

European-Non Finnish (NFE) AF: 0.0462 AC: 2455 AN: 53158

Other (OTH) AF: 0.139 AC: 213 AN: 1532

Alfa AF: 0.0941 Hom.: 7087

Bravo AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		0.30
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: rs732946; hg19: chrX-21985964;