X-21967056-T-TTTTA

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_50-104dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (724 hom., 2697 hem., cov: 0)
  • Exomes 𝑓: 0.073 (735 hom. 3424 hem.)
  • Failed GnomAD Quality Control
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0770

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-T-TTTTA is Benign according to our data. Variant chrX-21967056-T-TTTTA is described in ClinVar as [Benign]. Clinvar id is 1298255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMS	NM_004595.5	c.50-107_50-104dup		intron_variant		ENST00000404933.7
SMS	NM_001258423.2	c.50-107_50-104dup		intron_variant
SMS	XM_005274582.3	c.-53-107_-53-104dup		intron_variant
SMS	XM_011545568.3	c.-53-107_-53-104dup		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.140 AC: 12771 AN: 90907 Hom.: 726 Cov.: 0 AF XY: 0.136 AC XY: 2690 AN XY: 19727

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0444

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.0705

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0900

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.112

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0726 AC: 16719 AN: 230277 Hom.: 735 AF XY: 0.0727 AC XY: 3424 AN XY: 47085

Gnomad4 AFR exome AF: 0.0618

Gnomad4 AMR exome AF: 0.0513

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.0478

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0651

GnomAD4 genome AF: 0.141 AC: 12773 AN: 90904 Hom.: 724 Cov.: 0 AF XY: 0.137 AC XY: 2697 AN XY: 19750

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.0705

Gnomad4 EAS AF: 0.0343

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.112

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

Apr 03, 2021

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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: rs565160089; hg19: chrX-21985174;