rs1050755

chr10-110293841-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SMNDC1	NM_005871.4	c.*309G>A		3_prime_UTR_variant	6/6	ENST00000369603.10
SMNDC1	XM_047424438.1	c.*309G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMNDC1	ENST00000369603.10	c.*309G>A		3_prime_UTR_variant	6/6	1	NM_005871.4	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74068 AN: 151960 Hom.: 21770 Cov.: 32

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.: 0 AF XY: 0.590 AC XY: 8688 AN XY: 14730

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.487 AC: 74062 AN: 152080 Hom.: 21766 Cov.: 32 AF XY: 0.500 AC XY: 37191 AN XY: 74336

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.505

Alfa AF: 0.568 Hom.: 32561

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
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs1050755; hg19: chr10-112053599;