X-21967073-TTTATTTATTTATTTATTTAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004595.5(SMS):​c.50-108_50-89del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 349,806 control chromosomes in the GnomAD database, including 6,045 homozygotes. There are 19,522 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 928 hom., 3730 hem., cov: 16)
Exomes 𝑓: 0.25 ( 5117 hom. 15792 hem. )

Consequence

SMS
NM_004595.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant X-21967073-TTTATTTATTTATTTATTTAC-T is Benign according to our data. Variant chrX-21967073-TTTATTTATTTATTTATTTAC-T is described in ClinVar as [Benign]. Clinvar id is 1180100.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMSNM_004595.5 linkuse as main transcriptc.50-108_50-89del intron_variant ENST00000404933.7 NP_004586.2
SMSNM_001258423.2 linkuse as main transcriptc.50-108_50-89del intron_variant NP_001245352.1
SMSXM_005274582.3 linkuse as main transcriptc.-53-108_-53-89del intron_variant XP_005274639.1
SMSXM_011545568.3 linkuse as main transcriptc.-53-108_-53-89del intron_variant XP_011543870.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMSENST00000404933.7 linkuse as main transcriptc.50-108_50-89del intron_variant 1 NM_004595.5 ENSP00000385746 P1P52788-1
SMSENST00000379404.5 linkuse as main transcriptc.50-108_50-89del intron_variant 3 ENSP00000368714 P52788-2
SMSENST00000457085.2 linkuse as main transcriptc.395-108_395-89del intron_variant 5 ENSP00000407366
SMSENST00000478094.1 linkuse as main transcriptn.97-108_97-89del intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.165
AC:
14969
AN:
90846
Hom.:
928
Cov.:
16
AF XY:
0.169
AC XY:
3728
AN XY:
22078
show subpopulations
Gnomad AFR
AF:
0.139
Gnomad AMI
AF:
0.220
Gnomad AMR
AF:
0.127
Gnomad ASJ
AF:
0.113
Gnomad EAS
AF:
0.0210
Gnomad SAS
AF:
0.0396
Gnomad FIN
AF:
0.206
Gnomad MID
AF:
0.121
Gnomad NFE
AF:
0.194
Gnomad OTH
AF:
0.161
GnomAD4 exome
AF:
0.249
AC:
64612
AN:
258969
Hom.:
5117
AF XY:
0.331
AC XY:
15792
AN XY:
47683
show subpopulations
Gnomad4 AFR exome
AF:
0.159
Gnomad4 AMR exome
AF:
0.163
Gnomad4 ASJ exome
AF:
0.150
Gnomad4 EAS exome
AF:
0.0422
Gnomad4 SAS exome
AF:
0.114
Gnomad4 FIN exome
AF:
0.272
Gnomad4 NFE exome
AF:
0.268
Gnomad4 OTH exome
AF:
0.232
GnomAD4 genome
AF:
0.165
AC:
14963
AN:
90837
Hom.:
928
Cov.:
16
AF XY:
0.169
AC XY:
3730
AN XY:
22095
show subpopulations
Gnomad4 AFR
AF:
0.139
Gnomad4 AMR
AF:
0.127
Gnomad4 ASJ
AF:
0.113
Gnomad4 EAS
AF:
0.0210
Gnomad4 SAS
AF:
0.0393
Gnomad4 FIN
AF:
0.206
Gnomad4 NFE
AF:
0.194
Gnomad4 OTH
AF:
0.159
Alfa
AF:
0.160
Hom.:
787
Asia WGS
AF:
0.0410
AC:
103
AN:
2443

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 submitterclinical testingGeneDxMay 16, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs765255793; hg19: chrX-21985191; API