X-21990866-C-T

Variant names:

• chrX-21990866-C-T
• rs5951678
• NM_004595.5:c.946-1731C>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.946-1731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 111,751 control chromosomes in the GnomAD database, including 6,708 homozygotes. There are 11,247 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 0.35 (6708 hom., 11247 hem., cov: 24)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 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.946-1731C>T		intron	N/A	NP_004586.2
	SMS	NM_001258423.2		c.787-1731C>T		intron	N/A	NP_001245352.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	ENST00000404933.7	TSL:1 MANE Select	c.946-1731C>T		intron	N/A	ENSP00000385746.2
	SMS	ENST00000853889.1		c.964-1731C>T		intron	N/A	ENSP00000523948.1
	SMS	ENST00000955899.1		c.964-1731C>T		intron	N/A	ENSP00000625958.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 38722 AN: 111696 Hom.: 6700 Cov.: 24

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.347 AC: 38782 AN: 111751 Hom.: 6708 Cov.: 24 AF XY: 0.331 AC XY: 11247 AN XY: 33975

African (AFR) AF: 0.689 AC: 21100 AN: 30603

American (AMR) AF: 0.210 AC: 2228 AN: 10625

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 693 AN: 2647

East Asian (EAS) AF: 0.151 AC: 540 AN: 3576

South Asian (SAS) AF: 0.160 AC: 438 AN: 2739

European-Finnish (FIN) AF: 0.233 AC: 1402 AN: 6021

Middle Eastern (MID) AF: 0.222 AC: 48 AN: 216

European-Non Finnish (NFE) AF: 0.221 AC: 11740 AN: 53115

Other (OTH) AF: 0.310 AC: 474 AN: 1529

Alfa AF: 0.267 Hom.: 24868

Bravo AF: 0.362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.33
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: rs5951678; hg19: chrX-22008984;