Genetic Variant SPRN:p.Gly140Ser (chr10-133423264-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001391974.1(SPRN):c.418G>A(p.Gly140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,497,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SPRN
NM_001391974.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

Publications

0 publications found

Variant links:

Genes affected

SPRN (HGNC:16871): (shadow of prion protein) Predicted to enable nucleic acid binding activity. Predicted to be involved in protein import into nucleus. Predicted to be located in membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09004021).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391974.1. 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
	SPRN	NM_001391974.1	MANE Select	c.418G>A	p.Gly140Ser	missense	Exon 2 of 2	NP_001378903.1	Q5BIV9
	SPRN	NM_001012508.6		c.418G>A	p.Gly140Ser	missense	Exon 2 of 2	NP_001012526.2	Q5BIV9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPRN	ENST00000685335.1	MANE Select	c.418G>A	p.Gly140Ser	missense	Exon 2 of 2	ENSP00000510252.1	Q5BIV9
SPRN	ENST00000414069.2	TSL:1	c.418G>A	p.Gly140Ser	missense	Exon 2 of 2	ENSP00000433712.1	Q5BIV9
SPRN	ENST00000949115.1		c.418G>A	p.Gly140Ser	missense	Exon 2 of 2	ENSP00000619174.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000988

AC:

AN:

101222

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1345486

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27848

American (AMR)

AF:

0.00

AC:

AN:

32430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23886

East Asian (EAS)

AF:

0.00

AC:

AN:

31376

South Asian (SAS)

AF:

0.0000133

AC:

AN:

75298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5162

European-Non Finnish (NFE)

AF:

9.44e-7

AC:

AN:

1058894

Other (OTH)

AF:

0.00

AC:

AN:

55952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

PhyloP100

-0.031

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

REVEL

Benign

0.016

Sift

Benign

0.081

Sift4G

Uncertain

0.021

Polyphen

0.13

Vest4

0.14

MutPred

0.27

Gain of glycosylation at G140 (P = 0.037)

MVP

0.030

ClinPred

0.14

GERP RS

1.6

Varity_R

0.073

gMVP

0.076

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over