Genetic Variant SMS:c.170+530C>T (chrX-21967846-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004595.5(SMS):c.170+530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 111,970 control chromosomes in the GnomAD database, including 2,391 homozygotes. There are 5,127 hemizygotes in GnomAD. 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 0.16 ( 2391 hom., 5127 hem., cov: 23)

Consequence

SMS
NM_004595.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

1 publications found

Variant links:

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

SMS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5 link	c.170+530C>T	intron_variant	Intron 2 of 10	ENST00000404933.7	NP_004586.2	P52788-1
SMS	NM_001258423.2 link	c.170+530C>T	intron_variant	Intron 2 of 8		NP_001245352.1	P52788-2
SMS	XM_005274582.3 link	c.68+530C>T	intron_variant	Intron 2 of 10		XP_005274639.1
SMS	XM_011545568.3 link	c.68+530C>T	intron_variant	Intron 2 of 10		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMS	ENST00000404933.7 link	c.170+530C>T	intron_variant	Intron 2 of 10	1	NM_004595.5	ENSP00000385746.2	P52788-1
SMS	ENST00000457085.2 link	c.515+530C>T	intron_variant	Intron 2 of 5	5		ENSP00000407366.2	H7C2R7
SMS	ENST00000379404.5 link	c.170+530C>T	intron_variant	Intron 2 of 8	3		ENSP00000368714.1	P52788-2
SMS	ENST00000478094.1 link	n.217+530C>T	intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

18221

AN:

111919

Hom.:

2386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.00296

Gnomad AMR

AF:

0.0856

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00951

Gnomad SAS

AF:

0.0893

Gnomad FIN

AF:

0.0472

Gnomad MID

AF:

0.109

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.132

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

GnomAD4 genome

AF:

0.163

AC:

18251

AN:

111970

Hom.:

2391

Cov.:

AF XY:

0.150

AC XY:

5127

AN XY:

34154

show subpopulations

African (AFR)

AF:

0.449

AC:

13773

AN:

30675

American (AMR)

AF:

0.0854

AC:

912

AN:

10677

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

305

AN:

2655

East Asian (EAS)

AF:

0.00954

AC:

AN:

3564

South Asian (SAS)

AF:

0.0907

AC:

246

AN:

2713

European-Finnish (FIN)

AF:

0.0472

AC:

288

AN:

6103

Middle Eastern (MID)

AF:

0.106

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0462

AC:

2455

AN:

53158

Other (OTH)

AF:

0.139

AC:

213

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

435

869

1304

1738

2173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0941

Hom.:

7087

Bravo

AF:

0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.4

(source)

DANN

Benign

0.69

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over