NM_006714.5:c.152C>A

Variant names:

• chr6-122795716-C-A
• rs770665936
• NM_006714.5:c.152C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006714.5(SMPDL3A):​c.152C>A​(p.Thr51Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T51I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMPDL3A NM_006714.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

SMPDL3A (HGNC:17389): (sphingomyelin phosphodiesterase acid like 3A) Enables phosphoric diester hydrolase activity and zinc ion binding activity. Involved in nucleoside triphosphate catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SMPDL3A Gene-Disease associations (from GenCC):

• sensory peripheral neuropathy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000294893 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006714.5. 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
	SMPDL3A	NM_006714.5	MANE Select	c.152C>A	p.Thr51Asn	missense	Exon 2 of 8	NP_006705.1	Q92484-1
	SMPDL3A	NM_001286138.2		c.-67-1108C>A		intron	N/A	NP_001273067.1	Q92484-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMPDL3A	ENST00000368440.5	TSL:1 MANE Select	c.152C>A	p.Thr51Asn	missense	Exon 2 of 8	ENSP00000357425.4	Q92484-1
	SMPDL3A	ENST00000894537.1		c.152C>A	p.Thr51Asn	missense	Exon 2 of 7	ENSP00000564596.1
	SMPDL3A	ENST00000894534.1		c.152C>A	p.Thr51Asn	missense	Exon 2 of 6	ENSP00000564593.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.27	N
REVEL	Uncertain	0.32
Sift	Benign	0.57	T
Sift4G	Benign	0.82	T
Polyphen		0.96	D
Vest4		0.53
MutPred		0.43		Loss of glycosylation at T51 (P = 0.0587)
MVP		0.85
MPC		0.43
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.30
gMVP		0.57
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs770665936; hg19: chr6-123116861;