Variant chr1-27953319-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014474.4(SMPDL3B):c.478C>A(p.Pro160Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMPDL3B
NM_014474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

SMPDL3B (HGNC:21416): (sphingomyelin phosphodiesterase acid like 3B) Enables phosphoric diester hydrolase activity. Predicted to be involved in membrane lipid catabolic process; negative regulation of inflammatory response; and negative regulation of toll-like receptor signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SMPDL3B links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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/exons	MANE
SMPDL3B	NM_014474.4 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	4/8	ENST00000373894.8
SMPDL3B	NM_001009568.3 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	4/7
SMPDL3B	XM_011541259.3 linkuse as main transcript	c.568C>A	p.Pro190Thr	missense_variant	5/9
SMPDL3B	NM_001304579.2 linkuse as main transcript	c.-141C>A		5_prime_UTR_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPDL3B	ENST00000373894.8 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	4/8	1	NM_014474.4	P1	Q92485-1
	ENST00000448015.1 linkuse as main transcript	n.286+2452G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.478C>A (p.P160T) alteration is located in exon 4 (coding exon 4) of the SMPDL3B gene. This alteration results from a C to A substitution at nucleotide position 478, causing the proline (P) at amino acid position 160 to be replaced by a threonine (T). 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

Benign

0.12

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;D;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.6

M;.;M

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.017

D;D;T

Sift4G

Benign

0.14

T;D;T

Polyphen

0.88

P;.;P

Vest4

0.47

MutPred

0.59

Loss of stability (P = 0.0303);.;Loss of stability (P = 0.0303);

MVP

0.96

MPC

0.76

ClinPred

0.97

GERP RS

4.3

Varity_R

0.39

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over