X-21981473-A-T

Variant names:

• chrX-21981473-A-T
• rs5904598
• NM_004595.5:c.750+2507A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004595.5(SMS):​c.750+2507A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (19011 hom., 22954 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: SMS NM_004595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 1 publications found

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]

SMS Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Snyder type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5	c.750+2507A>T		intron_variant	Intron 7 of 10	ENST00000404933.7	NP_004586.2
SMS	NM_001258423.2	c.591+2507A>T		intron_variant	Intron 5 of 8		NP_001245352.1
SMS	XM_005274582.3	c.648+2507A>T		intron_variant	Intron 7 of 10		XP_005274639.1
SMS	XM_011545568.3	c.648+2507A>T		intron_variant	Intron 7 of 10		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMS	ENST00000404933.7	c.750+2507A>T		intron_variant	Intron 7 of 10	1	NM_004595.5	ENSP00000385746.2
SMS	ENST00000379404.5	c.591+2507A>T		intron_variant	Intron 5 of 8	3		ENSP00000368714.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 76724 AN: 110256 Hom.: 19013 Cov.: 23

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.703

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.696 AC: 76738 AN: 110311 Hom.: 19011 Cov.: 23 AF XY: 0.701 AC XY: 22954 AN XY: 32763

African (AFR) AF: 0.556 AC: 16901 AN: 30393

American (AMR) AF: 0.804 AC: 8307 AN: 10326

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 1850 AN: 2639

East Asian (EAS) AF: 0.815 AC: 2843 AN: 3488

South Asian (SAS) AF: 0.891 AC: 2332 AN: 2616

European-Finnish (FIN) AF: 0.759 AC: 4376 AN: 5766

Middle Eastern (MID) AF: 0.708 AC: 150 AN: 212

European-Non Finnish (NFE) AF: 0.729 AC: 38415 AN: 52685

Other (OTH) AF: 0.708 AC: 1076 AN: 1520

Alfa AF: 0.545 Hom.: 2210

Bravo AF: 0.693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.32
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5904598; hg19: chrX-21999591;