Variant 5-70925229-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000344.4(SMN1):c.81+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.79 ( 5 hom., cov: 0)

Exomes 𝑓: 0.081 ( 481 hom. )

Failed GnomAD Quality Control

Consequence

SMN1
NM_000344.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.377

Variant links:

Genes affected

SMN1 (HGNC:11117): (survival of motor neuron 1, telomeric) This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric and centromeric copies of this gene are nearly identical and encode the same protein. However, mutations in this gene, the telomeric copy, are associated with spinal muscular atrophy; mutations in the centromeric copy do not lead to disease. The centromeric copy may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3-8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene. The protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2014]

SMN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 5-70925229-C-T is Benign according to our data. Variant chr5-70925229-C-T is described in ClinVar as [Benign]. Clinvar id is 1279988.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMN1	NM_000344.4 link	c.81+45C>T		intron_variant		ENST00000380707.9	NP_000335.1	Q16637-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMN1	ENST00000380707.9 link	c.81+45C>T		intron_variant		1	NM_000344.4	ENSP00000370083.4		Q16637-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.900

Gnomad EAS

AF:

0.00

GnomAD3 exomes

AF:

0.146

AC:

543

AN:

3728

Hom.:

161

AF XY:

0.108

AC XY:

225

AN XY:

2076

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.0620

Gnomad ASJ exome

AF:

0.0854

Gnomad EAS exome

AF:

0.00345

Gnomad SAS exome

AF:

0.00674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0603

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0810

AC:

1624

AN:

20038

Hom.:

481

Cov.:

AF XY:

0.0672

AC XY:

715

AN XY:

10638

show subpopulations

Gnomad4 AFR exome

AF:

0.732

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.00236

Gnomad4 SAS exome

AF:

0.00976

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00953

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.786

AC:

AN:

Hom.:

Cov.:

AF XY:

0.800

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR

AF:

0.917

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:

0.163

Hom.:

818

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

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.0

DANN

Benign

0.80

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

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