10-110292931-C-G

Variant names:

• chr10-110292931-C-G
• rs10787227
• NM_005871.4:c.*1219G>C

Variant summary

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

The NM_005871.4(SMNDC1):​c.*1219G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,074 control chromosomes in the GnomAD database, including 14,401 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 0.39 (14401 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMNDC1 NM_005871.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMNDC1	NM_005871.4	c.*1219G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000369603.10	NP_005862.1
SMNDC1	XM_047424438.1	c.*1219G>C		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	c.*1219G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_005871.4	ENSP00000358616.4

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59455 AN: 151956 Hom.: 14395 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.406

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.391 AC: 59460 AN: 152074 Hom.: 14401 Cov.: 32 AF XY: 0.398 AC XY: 29603 AN XY: 74342

Gnomad4 AFR AF: 0.0947

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.402

Alfa AF: 0.432 Hom.: 2110

Bravo AF: 0.378

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.44
DANN	Benign	0.61

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: rs10787227; hg19: chr10-112052689;