rs575339975

Variant names:

• chr10-133423503-G-A
• rs575339975
• NM_001391974.1:c.179C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133423503-G-A
• chr10-133423503-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001391974.1(SPRN):​c.179C>T​(p.Pro60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,170,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: SPRN NM_001391974.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.413
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050333798).

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.179C>T	p.Pro60Leu	missense	Exon 2 of 2	NP_001378903.1	Q5BIV9
	SPRN	NM_001012508.6		c.179C>T	p.Pro60Leu	missense	Exon 2 of 2	NP_001012526.2	Q5BIV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRN	ENST00000685335.1	MANE Select	c.179C>T	p.Pro60Leu	missense	Exon 2 of 2	ENSP00000510252.1	Q5BIV9
	SPRN	ENST00000414069.2	TSL:1	c.179C>T	p.Pro60Leu	missense	Exon 2 of 2	ENSP00000433712.1	Q5BIV9
	SPRN	ENST00000949115.1		c.179C>T	p.Pro60Leu	missense	Exon 2 of 2	ENSP00000619174.1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 16 AN: 147862 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000600

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000391 AC: 4 AN: 1022614 Hom.: 0 Cov.: 29 AF XY: 0.00000206 AC XY: 1 AN XY: 486358

African (AFR) AF: 0.0000984 AC: 2 AN: 20330

American (AMR) AF: 0.00 AC: 0 AN: 6162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11080

East Asian (EAS) AF: 0.00 AC: 0 AN: 20694

South Asian (SAS) AF: 0.00 AC: 0 AN: 19368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2576

European-Non Finnish (NFE) AF: 0.00000226 AC: 2 AN: 885794

Other (OTH) AF: 0.00 AC: 0 AN: 38858

GnomAD4 genome AF: 0.000108 AC: 16 AN: 147968 Hom.: 0 Cov.: 32 AF XY: 0.000111 AC XY: 8 AN XY: 72140

African (AFR) AF: 0.000293 AC: 12 AN: 40910

American (AMR) AF: 0.00 AC: 0 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4940

South Asian (SAS) AF: 0.00 AC: 0 AN: 4620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000600 AC: 4 AN: 66658

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000125

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.41
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.015
Sift	Uncertain	0.021	D
Sift4G	Benign	0.25	T
Polyphen		0.11	B
Vest4		0.085
MutPred		0.20		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.048
ClinPred		0.15	T
GERP RS		2.8
Varity_R		0.052
gMVP		0.073
Mutation Taster		=100/0	polymorphism

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: rs575339975; hg19: chr10-135237007;