X-21990866-C-T

Variant names:

• chrX-21990866-C-T
• rs5951678
• NM_004595.5:c.946-1731C>T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5	c.946-1731C>T		intron_variant	Intron 9 of 10	ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.787-1731C>T		intron_variant	Intron 7 of 8		NP_001245352.1
SMS	XM_005274582.3	c.844-1731C>T		intron_variant	Intron 9 of 10		XP_005274639.1
SMS	XM_011545568.3	c.844-1731C>T		intron_variant	Intron 9 of 10		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.946-1731C>T		intron_variant	Intron 9 of 10	1	NM_004595.5	ENSP00000385746.2
SMS	ENST00000379404.5	c.787-1731C>T		intron_variant	Intron 7 of 8	3		ENSP00000368714.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 38722 AN: 111696 Hom.: 6700 Cov.: 24 AF XY: 0.330 AC XY: 11199 AN XY: 33910

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

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.310

Alfa AF: 0.233 Hom.: 15742

Bravo AF: 0.362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.81

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: rs5951678; hg19: chrX-22008984;