dbSNP rs1050755: SMNDC1:c.*309G>A (chr10-110293841-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005871.4(SMNDC1):c.*309G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 180,782 control chromosomes in the GnomAD database, including 26,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 21766 hom., cov: 32)

Exomes 𝑓: 0.59 ( 5232 hom. )

Consequence

SMNDC1
NM_005871.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

20 publications found

Variant links:

Genes affected

SMNDC1 (HGNC:16900): (survival motor neuron domain containing 1) This gene is a paralog of SMN1 gene, which encodes the survival motor neuron protein, mutations in which are cause of autosomal recessive proximal spinal muscular atrophy. The protein encoded by this gene is a nuclear protein that has been identified as a constituent of the spliceosome complex. This gene is differentially expressed, with abundant levels in skeletal muscle, and may share similar cellular function as the SMN1 gene. [provided by RefSeq, Jul 2008]

SMNDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMNDC1	NM_005871.4 link	c.*309G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000369603.10	NP_005862.1	O75940
SMNDC1	XM_047424438.1 link	c.*309G>A		3_prime_UTR_variant	Exon 6 of 6		XP_047280394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMNDC1	ENST00000369603.10 link	c.*309G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_005871.4	ENSP00000358616.4		O75940
SMNDC1	ENST00000369592.1 link	c.*309G>A		downstream_gene_variant		3		ENSP00000358605.1		O75940

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

74068

AN:

151960

Hom.:

21770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.840

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.510

GnomAD4 exome

AF:

0.586

AC:

16830

AN:

28702

Hom.:

5232

Cov.:

AF XY:

0.590

AC XY:

8688

AN XY:

14730

show subpopulations

African (AFR)

AF:

0.154

AC:

190

AN:

1232

American (AMR)

AF:

0.614

AC:

705

AN:

1148

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

734

AN:

1274

East Asian (EAS)

AF:

0.829

AC:

1427

AN:

1722

South Asian (SAS)

AF:

0.689

AC:

379

AN:

550

European-Finnish (FIN)

AF:

0.695

AC:

946

AN:

1362

Middle Eastern (MID)

AF:

0.479

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.586

AC:

11345

AN:

19352

Other (OTH)

AF:

0.540

AC:

1037

AN:

1922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

311

621

932

1242

1553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.487

AC:

74062

AN:

152080

Hom.:

21766

Cov.:

AF XY:

0.500

AC XY:

37191

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.143

AC:

5935

AN:

41484

American (AMR)

AF:

0.614

AC:

9382

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2124

AN:

3466

East Asian (EAS)

AF:

0.840

AC:

4359

AN:

5190

South Asian (SAS)

AF:

0.687

AC:

3312

AN:

4824

European-Finnish (FIN)

AF:

0.674

AC:

7125

AN:

10572

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40111

AN:

67936

Other (OTH)

AF:

0.505

AC:

1068

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1570

3140

4711

6281

7851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.557

Hom.:

39669

Bravo

AF:

0.466

Asia WGS

AF:

0.655

AC:

2274

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.68

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over