Variant chr5-70925090-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000344.4(SMN1):c.-14C>T variant causes a 5 prime UTR 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 0.50 ( 510 hom., cov: 1)

Exomes 𝑓: 0.076 ( 825 hom. )

Failed GnomAD Quality Control

Consequence

SMN1
NM_000344.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.685

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMN1	NM_000344.4 link	c.-14C>T		5_prime_UTR_variant	1/9	ENST00000380707.9	NP_000335.1	Q16637-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMN1	ENST00000380707 link	c.-14C>T		5_prime_UTR_variant	1/9	1	NM_000344.4	ENSP00000370083.4		Q16637-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1248

AN:

2502

Hom.:

501

Cov.:

FAILED QC

Gnomad AFR

AF:

0.838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.0238

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0226

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.153

AC:

903

AN:

5906

Hom.:

271

AF XY:

0.119

AC XY:

379

AN XY:

3182

show subpopulations

Gnomad AFR exome

AF:

0.723

Gnomad AMR exome

AF:

0.0586

Gnomad ASJ exome

AF:

0.0931

Gnomad EAS exome

AF:

0.00638

Gnomad SAS exome

AF:

0.00680

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0562

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0763

AC:

2673

AN:

35014

Hom.:

825

Cov.:

AF XY:

0.0637

AC XY:

1188

AN XY:

18662

show subpopulations

Gnomad4 AFR exome

AF:

0.739

Gnomad4 AMR exome

AF:

0.0760

Gnomad4 ASJ exome

AF:

0.0927

Gnomad4 EAS exome

AF:

0.00664

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00891

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.505

AC:

1267

AN:

2510

Hom.:

510

Cov.:

AF XY:

0.504

AC XY:

550

AN XY:

1092

show subpopulations

Gnomad4 AFR

AF:

0.840

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.0238

Gnomad4 SAS

AF:

0.0625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.131

Hom.:

522

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

-0.86

CADD

Benign

4.3

DANN

Benign

0.96

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