10-110292931-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMNDC1	NM_005871.4	MANE Select	c.*1219G>C		3_prime_UTR	Exon 6 of 6	NP_005862.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMNDC1	ENST00000369603.10	TSL:1 MANE Select	c.*1219G>C		3_prime_UTR	Exon 6 of 6	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0947 AC: 3931 AN: 41518

American (AMR) AF: 0.535 AC: 8168 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2874 AN: 5168

South Asian (SAS) AF: 0.362 AC: 1743 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 6019 AN: 10562

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33822 AN: 67956

Other (OTH) AF: 0.402 AC: 848 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.44
DANN	Benign	0.61
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10787227; hg19: chr10-112052689;