X-21966875-G-A

Position:

• chrX-21966875-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004595.5(SMS):​c.50-321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 108,912 control chromosomes in the GnomAD database, including 3,286 homozygotes. There are 8,481 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (3286 hom., 8481 hem., cov: 22)
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-21966875-G-A is Benign according to our data. Variant chrX-21966875-G-A is described in ClinVar as [Benign]. Clinvar id is 1269916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMS	NM_004595.5	c.50-321G>A		intron_variant		ENST00000404933.7
SMS	NM_001258423.2	c.50-321G>A		intron_variant
SMS	XM_005274582.3	c.-53-321G>A		intron_variant
SMS	XM_011545568.3	c.-53-321G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMS	ENST00000404933.7	c.50-321G>A		intron_variant		1	NM_004595.5	P1
SMS	ENST00000379404.5	c.50-321G>A		intron_variant		3
SMS	ENST00000457085.2	c.395-321G>A		intron_variant		5
SMS	ENST00000478094.1	n.97-321G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 30633 AN: 108873 Hom.: 3285 Cov.: 22 AF XY: 0.271 AC XY: 8462 AN XY: 31273

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 30650 AN: 108912 Hom.: 3286 Cov.: 22 AF XY: 0.271 AC XY: 8481 AN XY: 31322

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.289

Alfa AF: 0.292 Hom.: 20391

Bravo AF: 0.299

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

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7059727; hg19: chrX-21984993;