10-133423288-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001391974.1(SPRN):​c.394G>A​(p.Gly132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000857 in 1,517,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

SPRN
NM_001391974.1 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033278465).
BP6
Variant 10-133423288-C-T is Benign according to our data. Variant chr10-133423288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2273690.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPRNNM_001391974.1 linkc.394G>A p.Gly132Ser missense_variant Exon 2 of 2 ENST00000685335.1 NP_001378903.1
SPRNNM_001012508.6 linkc.394G>A p.Gly132Ser missense_variant Exon 2 of 2 NP_001012526.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPRNENST00000685335.1 linkc.394G>A p.Gly132Ser missense_variant Exon 2 of 2 NM_001391974.1 ENSP00000510252.1 Q5BIV9
SPRNENST00000414069.2 linkc.394G>A p.Gly132Ser missense_variant Exon 2 of 2 1 ENSP00000433712.1 Q5BIV9

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152074
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000659
AC:
9
AN:
1365444
Hom.:
0
Cov.:
29
AF XY:
0.0000104
AC XY:
7
AN XY:
673702
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:
0.0000130
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000748
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152074
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 26, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.0020
DANN
Benign
0.80
DEOGEN2
Benign
0.0060
T
Eigen
Benign
-2.6
Eigen_PC
Benign
-2.6
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.41
N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.0090
Sift
Benign
0.83
T
Sift4G
Benign
0.63
T
Polyphen
0.0020
B
Vest4
0.077
MutPred
0.17
Loss of sheet (P = 0.0457);
MVP
0.014
ClinPred
0.061
T
GERP RS
-7.8
Varity_R
0.038
gMVP
0.031

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755980014; hg19: chr10-135236792; API