Genetic Variant SPRN:p.Gly132Cys (chr10-133423288-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001391974.1(SPRN):c.394G>T(p.Gly132Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. G132D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPRN
NM_001391974.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.34

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047481805).

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.394G>T	p.Gly132Cys	missense	Exon 2 of 2	NP_001378903.1	Q5BIV9
	SPRN	NM_001012508.6		c.394G>T	p.Gly132Cys	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.394G>T	p.Gly132Cys	missense	Exon 2 of 2	ENSP00000510252.1	Q5BIV9
SPRN	ENST00000414069.2	TSL:1	c.394G>T	p.Gly132Cys	missense	Exon 2 of 2	ENSP00000433712.1	Q5BIV9
SPRN	ENST00000949115.1		c.394G>T	p.Gly132Cys	missense	Exon 2 of 2	ENSP00000619174.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000888

AC:

AN:

112626

AF XY:

0.0000160

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1365444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673702

African (AFR)

AF:

0.00

AC:

AN:

28800

American (AMR)

AF:

0.00

AC:

AN:

34120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24408

East Asian (EAS)

AF:

0.00

AC:

AN:

33192

South Asian (SAS)

AF:

0.00

AC:

AN:

76870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070124

Other (OTH)

AF:

0.00

AC:

AN:

57062

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000218

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0090

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0093

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.33

M_CAP

Benign

0.025

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-6.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.0

REVEL

Benign

0.021

Sift

Benign

0.13

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.13

MutPred

0.28

Loss of glycosylation at T130 (P = 0.0347)

MVP

0.014

ClinPred

0.050

GERP RS

-7.8

Varity_R

0.12

gMVP

0.043

Mutation Taster

=95/5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over