16-28981909-T-A

Position:

• chr16-28981909-T-A

Variant summary

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

The NM_032038.3(SPNS1):​c.818T>A​(p.Phe273Tyr) 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: 33)
• Consequence: SPNS1 NM_032038.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

Genes affected

SPNS1 (HGNC:30621): (SPNS lysolipid transporter 1, lysophospholipid) Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261067 (HGNC:):

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/exons	MANE	Protein	UniProt
SPNS1	NM_032038.3	c.818T>A	p.Phe273Tyr	missense_variant	7/12	ENST00000311008.16	NP_114427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS1	ENST00000311008.16	c.818T>A	p.Phe273Tyr	missense_variant	7/12	1	NM_032038.3	ENSP00000309945.11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.818T>A (p.F273Y) alteration is located in exon 7 (coding exon 7) of the SPNS1 gene. This alteration results from a T to A substitution at nucleotide position 818, causing the phenylalanine (F) at amino acid position 273 to be replaced by a tyrosine (Y). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	.;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.052
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;L;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.56	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.39	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.18, 0.15	.;B;B;.
Vest4		0.52
MutPred		0.74		.;Loss of stability (P = 0.0815);.;.;
MVP		0.28
MPC		1.2
ClinPred		0.83	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.89

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: chr16-28993230;