rs2040357

Positions:

• chrX-21960709-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004595.5(SMS):​c.50-6487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 110,642 control chromosomes in the GnomAD database, including 9,449 homozygotes. There are 14,252 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 0.45 (9449 hom., 14252 hem., cov: 23)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5	c.50-6487C>T		intron_variant		ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.50-6487C>T		intron_variant			NP_001245352.1
SMS	XM_005274582.3	c.-54+720C>T		intron_variant			XP_005274639.1
SMS	XM_011545568.3	c.-53-6487C>T		intron_variant			XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.50-6487C>T		intron_variant		1	NM_004595.5	ENSP00000385746.2
SMS	ENST00000457085.2	c.395-6487C>T		intron_variant		5		ENSP00000407366.2
SMS	ENST00000379404.5	c.50-6487C>T		intron_variant		3		ENSP00000368714.1
SMS	ENST00000478094.1	n.97-6487C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.446 AC: 49373 AN: 110594 Hom.: 9438 Cov.: 23 AF XY: 0.433 AC XY: 14214 AN XY: 32838

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.447 AC: 49425 AN: 110642 Hom.: 9449 Cov.: 23 AF XY: 0.433 AC XY: 14252 AN XY: 32896

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.424

Alfa AF: 0.389 Hom.: 3264

Bravo AF: 0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.80
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs2040357; hg19: chrX-21978827;