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:

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new If you want to explore the variant's impact on the transcript NM_005871.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMNDC1	NM_005871.4	MANE Select	c.*309G>A		3_prime_UTR	Exon 6 of 6	NP_005862.1	O75940

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMNDC1	ENST00000369603.10	TSL:1 MANE Select	c.*309G>A	3_prime_UTR	Exon 6 of 6	ENSP00000358616.4	O75940
SMNDC1	ENST00000889865.1		c.*309G>A	3_prime_UTR	Exon 7 of 7	ENSP00000559924.1
SMNDC1	ENST00000934673.1		c.*309G>A	3_prime_UTR	Exon 7 of 7	ENSP00000604732.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over