X-21967089-TTTAC-T

Variant summary

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

The NM_004595.5(SMS):c.50-103_50-100del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 220,733 control chromosomes in the GnomAD database, including 481 homozygotes. There are 4,395 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (197 hom., 1759 hem., cov: 0)
  • Exomes 𝑓: 0.071 (284 hom. 2636 hem.)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.929

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-21967089-TTTAC-T is Benign according to our data. Variant chrX-21967089-TTTAC-T is described in ClinVar as [Benign]. Clinvar id is 1271761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMS	NM_004595.5	c.50-103_50-100del		intron_variant		ENST00000404933.7
SMS	NM_001258423.2	c.50-103_50-100del		intron_variant
SMS	XM_005274582.3	c.-53-103_-53-100del		intron_variant
SMS	XM_011545568.3	c.-53-103_-53-100del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMS	ENST00000404933.7	c.50-103_50-100del		intron_variant		1	NM_004595.5	P1
SMS	ENST00000379404.5	c.50-103_50-100del		intron_variant		3
SMS	ENST00000457085.2	c.395-103_395-100del		intron_variant		5
SMS	ENST00000478094.1	n.97-103_97-100del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 6798 AN: 56851 Hom.: 196 Cov.: 0 AF XY: 0.0886 AC XY: 1756 AN XY: 19829

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0311

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.0712 AC: 11660 AN: 163874 Hom.: 284 AF XY: 0.0624 AC XY: 2636 AN XY: 42264

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0718

Gnomad4 SAS exome AF: 0.0411

Gnomad4 FIN exome AF: 0.0343

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0889

GnomAD4 genome AF: 0.120 AC: 6802 AN: 56859 Hom.: 197 Cov.: 0 AF XY: 0.0886 AC XY: 1759 AN XY: 19847

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72369541; hg19: chrX-21985207;