chr16-28984436-C-A

Variant names:

• chr16-28984436-C-A
• rs7140
• NM_032038.3:c.*137C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032038.3(SPNS1):​c.*137C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 854,248 control chromosomes in the GnomAD database, including 229,198 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 0.77 (45475 hom., cov: 34)
  • Exomes 𝑓: 0.72 (183723 hom.)
• Consequence: SPNS1 NM_032038.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.219226E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032038.3. 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
	SPNS1	NM_032038.3	MANE Select	c.*137C>A		3_prime_UTR	Exon 12 of 12	NP_114427.1
	SPNS1	NM_001142448.2		c.*137C>A		3_prime_UTR	Exon 13 of 13	NP_001135920.1
	SPNS1	NM_001142451.2		c.*137C>A		3_prime_UTR	Exon 11 of 11	NP_001135923.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS1	ENST00000311008.16	TSL:1 MANE Select	c.*137C>A		3_prime_UTR	Exon 12 of 12	ENSP00000309945.11
	SPNS1	ENST00000565975.5	TSL:1	c.*137C>A		3_prime_UTR	Exon 13 of 13	ENSP00000454360.1
	SPNS1	ENST00000334536.12	TSL:1	c.*137C>A		3_prime_UTR	Exon 11 of 11	ENSP00000335494.8

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116330 AN: 152056 Hom.: 45424 Cov.: 34

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.779

GnomAD2 exomes AF: 0.729 AC: 101296 AN: 138880 AF XY: 0.739

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.927

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.717 AC: 503712 AN: 702074 Hom.: 183723 Cov.: 9 AF XY: 0.722 AC XY: 267345 AN XY: 370072

African (AFR) AF: 0.920 AC: 17069 AN: 18550

American (AMR) AF: 0.559 AC: 19520 AN: 34898

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 17064 AN: 20906

East Asian (EAS) AF: 0.920 AC: 30156 AN: 32784

South Asian (SAS) AF: 0.807 AC: 52683 AN: 65268

European-Finnish (FIN) AF: 0.665 AC: 22617 AN: 34030

Middle Eastern (MID) AF: 0.866 AC: 3784 AN: 4372

European-Non Finnish (NFE) AF: 0.690 AC: 314217 AN: 455596

Other (OTH) AF: 0.746 AC: 26602 AN: 35670

GnomAD4 genome AF: 0.765 AC: 116427 AN: 152174 Hom.: 45475 Cov.: 34 AF XY: 0.764 AC XY: 56851 AN XY: 74390

African (AFR) AF: 0.913 AC: 37952 AN: 41554

American (AMR) AF: 0.654 AC: 10000 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4719 AN: 5156

South Asian (SAS) AF: 0.810 AC: 3903 AN: 4818

European-Finnish (FIN) AF: 0.673 AC: 7127 AN: 10594

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47279 AN: 67976

Other (OTH) AF: 0.780 AC: 1648 AN: 2112

Alfa AF: 0.724 Hom.: 79125

Bravo AF: 0.771

TwinsUK AF: 0.698 AC: 2587

ALSPAC AF: 0.691 AC: 2665

ExAC AF: 0.644 AC: 44792

Asia WGS AF: 0.825 AC: 2872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.5
DANN	Benign	0.90
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	7.2e-7	T
PhyloP100		-1.5
PROVEAN	Benign	-0.17	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
GERP RS		0.77
PromoterAI		-0.0048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7140; hg19: chr16-28995757;