X-21949439-C-T

Position:

• chrX-21949439-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.49+8566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 111,583 control chromosomes in the GnomAD database, including 1,801 homozygotes. There are 4,444 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 0.14 (1801 hom., 4444 hem., cov: 23)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5	c.49+8566C>T		intron_variant		ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.49+8566C>T		intron_variant			NP_001245352.1
SMS	XM_011545568.3	c.-54+8072C>T		intron_variant			XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.49+8566C>T		intron_variant		1	NM_004595.5	ENSP00000385746	P1
SMS	ENST00000379404.5	c.49+8566C>T		intron_variant		3		ENSP00000368714
SMS	ENST00000457085.2	c.394+8072C>T		intron_variant		5		ENSP00000407366
SMS	ENST00000478094.1	n.96+8566C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 16064 AN: 111531 Hom.: 1796 Cov.: 23 AF XY: 0.131 AC XY: 4436 AN XY: 33747

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.00292

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00811

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.144 AC: 16093 AN: 111583 Hom.: 1801 Cov.: 23 AF XY: 0.131 AC XY: 4444 AN XY: 33809

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00813

Gnomad4 SAS AF: 0.0725

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0465

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0560 Hom.: 307

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.61

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: rs5951672; hg19: chrX-21967557;