dbSNP rs2040357: SMS:c.50-6487C>T (chrX-21960709-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.50-6487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 110,642 control chromosomes in the GnomAD database, including 9,449 homozygotes. There are 14,252 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 0.45 ( 9449 hom., 14252 hem., cov: 23)

Consequence

SMS
NM_004595.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.735

Publications

3 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMS	NM_004595.5 link	c.50-6487C>T	intron_variant	Intron 1 of 10	ENST00000404933.7	NP_004586.2	P52788-1
SMS	NM_001258423.2 link	c.50-6487C>T	intron_variant	Intron 1 of 8		NP_001245352.1	P52788-2
SMS	XM_005274582.3 link	c.-54+720C>T	intron_variant	Intron 1 of 10		XP_005274639.1
SMS	XM_011545568.3 link	c.-53-6487C>T	intron_variant	Intron 1 of 10		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMS	ENST00000404933.7 link	c.50-6487C>T	intron_variant	Intron 1 of 10	1	NM_004595.5	ENSP00000385746.2	P52788-1
SMS	ENST00000457085.2 link	c.395-6487C>T	intron_variant	Intron 1 of 5	5		ENSP00000407366.2	H7C2R7
SMS	ENST00000379404.5 link	c.50-6487C>T	intron_variant	Intron 1 of 8	3		ENSP00000368714.1	P52788-2
SMS	ENST00000478094.1 link	n.97-6487C>T	intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

49373

AN:

110594

Hom.:

9438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.421

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

GnomAD4 genome

AF:

0.447

AC:

49425

AN:

110642

Hom.:

9449

Cov.:

AF XY:

0.433

AC XY:

14252

AN XY:

32896

show subpopulations

African (AFR)

AF:

0.747

AC:

22654

AN:

30321

American (AMR)

AF:

0.469

AC:

4861

AN:

10363

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

973

AN:

2632

East Asian (EAS)

AF:

0.308

AC:

1079

AN:

3500

South Asian (SAS)

AF:

0.172

AC:

461

AN:

2674

European-Finnish (FIN)

AF:

0.329

AC:

1933

AN:

5878

Middle Eastern (MID)

AF:

0.349

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.313

AC:

16559

AN:

52891

Other (OTH)

AF:

0.424

AC:

636

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

852

1704

2556

3408

4260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.389

Hom.:

3264

Bravo

AF:

0.476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.80

(source)

DANN

Benign

0.55

PhyloP100

-0.73

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