Variant X-21967209-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004595.5(SMS):c.63C>T(p.Thr21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,206,270 control chromosomes in the GnomAD database, including 2 homozygotes. There are 141 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., 26 hem., cov: 21)

Exomes 𝑓: 0.00036 ( 1 hom. 115 hem. )

Consequence

SMS
NM_004595.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.526

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant X-21967209-C-T is Benign according to our data. Variant chrX-21967209-C-T is described in ClinVar as [Benign]. Clinvar id is 792878.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.526 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 26 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMS	NM_004595.5 linkuse as main transcript	c.63C>T	p.Thr21=	synonymous_variant	2/11	ENST00000404933.7
SMS	NM_001258423.2 linkuse as main transcript	c.63C>T	p.Thr21=	synonymous_variant	2/9
SMS	XM_005274582.3 linkuse as main transcript	c.-40C>T		5_prime_UTR_variant	2/11
SMS	XM_011545568.3 linkuse as main transcript	c.-40C>T		5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMS	ENST00000404933.7 linkuse as main transcript	c.63C>T	p.Thr21=	synonymous_variant	2/11	1	NM_004595.5	P1	P52788-1
SMS	ENST00000457085.2 linkuse as main transcript	c.408C>T	p.Thr136=	synonymous_variant	2/6	5
SMS	ENST00000379404.5 linkuse as main transcript	c.63C>T	p.Thr21=	synonymous_variant	2/9	3			P52788-2
SMS	ENST00000478094.1 linkuse as main transcript	n.110C>T		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.000555

AC:

AN:

109977

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

32225

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00854

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.000681

GnomAD3 exomes

AF:

0.000803

AC:

147

AN:

183054

Hom.:

AF XY:

0.000740

AC XY:

AN XY:

67586

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00794

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000362

AC:

397

AN:

1096245

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

115

AN XY:

362101

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00798

Gnomad4 NFE exome

AF:

0.0000689

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000554

AC:

AN:

110025

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

32283

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00854

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.000702

Hom.:

Bravo

AF:

0.0000302

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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