Variant rs142264016 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_004595.5(SMS):c.330A>G(p.Arg110Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,207,732 control chromosomes in the GnomAD database, including 1 homozygotes. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 1 hom. 9 hem. )

Consequence

SMS
NM_004595.5 splice_region, synonymous

Scores

Splicing: ADA: 0.00003563

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0250

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 links:

SMS (HGNC:):

SMS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=-0.025 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMS	NM_004595.5 linkuse as main transcript	c.330A>G	p.Arg110Arg	splice_region_variant, synonymous_variant	5/11	ENST00000404933.7	NP_004586.2	P52788-1
SMS	NM_001258423.2 linkuse as main transcript	c.171A>G	p.Arg57Arg	splice_region_variant, synonymous_variant	3/9		NP_001245352.1	P52788-2
SMS	XM_005274582.3 linkuse as main transcript	c.228A>G	p.Arg76Arg	splice_region_variant, synonymous_variant	5/11		XP_005274639.1
SMS	XM_011545568.3 linkuse as main transcript	c.228A>G	p.Arg76Arg	splice_region_variant, synonymous_variant	5/11		XP_011543870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMS	ENST00000404933.7 linkuse as main transcript	c.330A>G	p.Arg110Arg	splice_region_variant, synonymous_variant	5/11	1	NM_004595.5	ENSP00000385746.2	P52788-1
SMS	ENST00000457085.2 linkuse as main transcript	c.675A>G	p.Arg225Arg	splice_region_variant, synonymous_variant	5/6	5		ENSP00000407366.2	H7C2R7
SMS	ENST00000379404.5 linkuse as main transcript	c.171A>G	p.Arg57Arg	splice_region_variant, synonymous_variant	3/9	3		ENSP00000368714.1	P52788-2
SMS	ENST00000478094.1 linkuse as main transcript	n.283A>G		splice_region_variant, non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.000428

AC:

AN:

112126

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

AN XY:

34284

show subpopulations

Gnomad AFR

AF:

0.00156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.000131

AC:

AN:

182851

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

67559

show subpopulations

Gnomad AFR exome

AF:

0.00183

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000374

AC:

AN:

1095555

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

361101

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.000428

AC:

AN:

112177

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

AN XY:

34345

show subpopulations

Gnomad4 AFR

AF:

0.00155

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000433

Hom.:

Bravo

AF:

0.000419

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 08, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.4

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over