X-21967085-TTTATTTAC-T

Position:

• chrX-21967085-TTTATTTAC-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_50-96delCTTATTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 274,712 control chromosomes in the GnomAD database, including 3,514 homozygotes. There are 10,797 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (2073 hom., 4710 hem., cov: 0)
  • Exomes 𝑓: 0.14 (1441 hom. 6087 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-21967085-TTTATTTAC-T is Benign according to our data. Variant chrX-21967085-TTTATTTAC-T is described in ClinVar as [Benign]. Clinvar id is 1272749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5	c.50-103_50-96delCTTATTTA		intron_variant		ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.50-103_50-96delCTTATTTA		intron_variant			NP_001245352.1
SMS	XM_005274582.3	c.-53-103_-53-96delCTTATTTA		intron_variant			XP_005274639.1
SMS	XM_011545568.3	c.-53-103_-53-96delCTTATTTA		intron_variant			XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.50-110_50-103delTTATTTAC		intron_variant		1	NM_004595.5	ENSP00000385746.2
SMS	ENST00000457085.2	c.395-110_395-103delTTATTTAC		intron_variant		5		ENSP00000407366.2
SMS	ENST00000379404.5	c.50-110_50-103delTTATTTAC		intron_variant		3		ENSP00000368714.1
SMS	ENST00000478094.1	n.97-110_97-103delTTATTTAC		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 19341 AN: 81114 Hom.: 2068 Cov.: 0 AF XY: 0.204 AC XY: 4704 AN XY: 23048

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.138 AC: 26662 AN: 193570 Hom.: 1441 AF XY: 0.136 AC XY: 6087 AN XY: 44844

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.239 AC: 19359 AN: 81142 Hom.: 2073 Cov.: 0 AF XY: 0.204 AC XY: 4710 AN XY: 23072

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.231

Alfa AF: 0.165 Hom.: 517

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 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs750466204; hg19: chrX-21985203;