10-110295299-C-T

Variant names:

• chr10-110295299-C-T
• NM_005871.4:c.508G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005871.4(SMNDC1):​c.508G>A​(p.Glu170Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMNDC1 NM_005871.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMNDC1	NM_005871.4	c.508G>A	p.Glu170Lys	missense_variant	Exon 5 of 6	ENST00000369603.10	NP_005862.1
SMNDC1	XM_047424438.1	c.391G>A	p.Glu131Lys	missense_variant	Exon 5 of 6		XP_047280394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMNDC1	ENST00000369603.10	c.508G>A	p.Glu170Lys	missense_variant	Exon 5 of 6	1	NM_005871.4	ENSP00000358616.4
SMNDC1	ENST00000369592.1	c.508G>A	p.Glu170Lys	missense_variant	Exon 5 of 6	3		ENSP00000358605.1
SMNDC1	ENST00000460483.5	n.684G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508G>A (p.E170K) alteration is located in exon 5 (coding exon 4) of the SMNDC1 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the glutamic acid (E) at amino acid position 170 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.22	T;T
Polyphen		0.75	P;P
Vest4		0.71
MutPred		0.28		Gain of MoRF binding (P = 0.0146);Gain of MoRF binding (P = 0.0146);
MVP		1.0
MPC		3.0
ClinPred		0.93	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.38
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-112055057;