X-21967056-TTTTA-T

Position:

• chrX-21967056-TTTTA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004595.5(SMS):​c.50-107_50-104del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 322,264 control chromosomes in the GnomAD database, including 188 homozygotes. There are 2,368 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (53 hom., 701 hem., cov: 0)
  • Exomes 𝑓: 0.031 (135 hom. 1667 hem.)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

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 -10 ACMG points.

• BP6: Variant X-21967056-TTTTA-T is Benign according to our data. Variant chrX-21967056-TTTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1804569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5	c.50-107_50-104del		intron_variant		ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.50-107_50-104del		intron_variant			NP_001245352.1
SMS	XM_005274582.3	c.-53-107_-53-104del		intron_variant			XP_005274639.1
SMS	XM_011545568.3	c.-53-107_-53-104del		intron_variant			XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.50-107_50-104del		intron_variant		1	NM_004595.5	ENSP00000385746	P1
SMS	ENST00000379404.5	c.50-107_50-104del		intron_variant		3		ENSP00000368714
SMS	ENST00000457085.2	c.395-107_395-104del		intron_variant		5		ENSP00000407366
SMS	ENST00000478094.1	n.97-107_97-104del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 3204 AN: 90978 Hom.: 54 Cov.: 0 AF XY: 0.0355 AC XY: 702 AN XY: 19756

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00635

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0284

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0284

GnomAD4 exome AF: 0.0308 AC: 7116 AN: 231289 Hom.: 135 AF XY: 0.0348 AC XY: 1667 AN XY: 47897

Gnomad4 AFR exome AF: 0.00883

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0320

Gnomad4 OTH exome AF: 0.0291

GnomAD4 genome AF: 0.0352 AC: 3200 AN: 90975 Hom.: 53 Cov.: 0 AF XY: 0.0354 AC XY: 701 AN XY: 19779

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0281

Bravo AF: 0.0304

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

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: rs565160089; hg19: chrX-21985174;