Genetic Variant NM_004595.5:c.111G>A (chrX-21967257-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_004595.5(SMS):c.111G>A(p.Glu37Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,714 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000091 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

SMS
NM_004595.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

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), PanelApp Australia, Orphanet, G2P, ClinGen

SMS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.054).

BP7

Synonymous conserved (PhyloP=2.37 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004595.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMS	NM_004595.5	MANE Select	c.111G>A	p.Glu37Glu	synonymous	Exon 2 of 11	NP_004586.2
	SMS	NM_001258423.2		c.111G>A	p.Glu37Glu	synonymous	Exon 2 of 9	NP_001245352.1	P52788-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMS	ENST00000404933.7	TSL:1 MANE Select	c.111G>A	p.Glu37Glu	synonymous	Exon 2 of 11	ENSP00000385746.2	P52788-1
SMS	ENST00000853889.1		c.111G>A	p.Glu37Glu	synonymous	Exon 2 of 12	ENSP00000523948.1
SMS	ENST00000955899.1		c.111G>A	p.Glu37Glu	synonymous	Exon 2 of 12	ENSP00000625958.1

Frequencies

GnomAD3 genomes

AF:

0.00000910

AC:

AN:

109877

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

183316

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1096837

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362247

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26374

American (AMR)

AF:

0.0000568

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19364

East Asian (EAS)

AF:

0.00

AC:

AN:

30176

South Asian (SAS)

AF:

0.00

AC:

AN:

54113

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40489

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4041

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841064

Other (OTH)

AF:

0.00

AC:

AN:

46022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000910

AC:

AN:

109877

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

32075

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30132

American (AMR)

AF:

0.0000984

AC:

AN:

10160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2623

East Asian (EAS)

AF:

0.00

AC:

AN:

3530

South Asian (SAS)

AF:

0.00

AC:

AN:

2556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52799

Other (OTH)

AF:

0.00

AC:

AN:

1470

Age Distribution

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.3

(source)

DANN

Benign

0.47

PhyloP100

2.4

Mutation Taster

=296/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over