rs1431961849

Variant names:

• chr10-133423474-C-G
• rs1431961849
• NM_001391974.1:c.208G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-133423474-C-G
• chr10-133423474-C-T
• chr10-133423474-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001391974.1(SPRN):​c.208G>C​(p.Gly70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,161,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G70A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SPRN NM_001391974.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.992
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.105359435).

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.208G>C	p.Gly70Arg	missense	Exon 2 of 2	NP_001378903.1	Q5BIV9
	SPRN	NM_001012508.6		c.208G>C	p.Gly70Arg	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.208G>C	p.Gly70Arg	missense	Exon 2 of 2	ENSP00000510252.1	Q5BIV9
	SPRN	ENST00000414069.2	TSL:1	c.208G>C	p.Gly70Arg	missense	Exon 2 of 2	ENSP00000433712.1	Q5BIV9
	SPRN	ENST00000949115.1		c.208G>C	p.Gly70Arg	missense	Exon 2 of 2	ENSP00000619174.1

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 6 AN: 148308 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000733

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 16 AN: 1012618 Hom.: 0 Cov.: 28 AF XY: 0.0000104 AC XY: 5 AN XY: 482710

African (AFR) AF: 0.00 AC: 0 AN: 19916

American (AMR) AF: 0.00 AC: 0 AN: 5834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10556

East Asian (EAS) AF: 0.00 AC: 0 AN: 19518

South Asian (SAS) AF: 0.000310 AC: 6 AN: 19328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2508

European-Non Finnish (NFE) AF: 0.00000682 AC: 6 AN: 879954

Other (OTH) AF: 0.000105 AC: 4 AN: 38174

GnomAD4 genome AF: 0.0000539 AC: 8 AN: 148414 Hom.: 0 Cov.: 32 AF XY: 0.0000552 AC XY: 4 AN XY: 72400

African (AFR) AF: 0.000122 AC: 5 AN: 41070

American (AMR) AF: 0.00 AC: 0 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66652

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.99
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.029
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.081	B
Vest4		0.21
MutPred		0.40		Gain of methylation at G70 (P = 0.003)
MVP		0.15
ClinPred		0.87	D
GERP RS		1.3
Varity_R		0.36
gMVP		0.11
Mutation Taster		=98/2	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: rs1431961849; hg19: chr10-135236978;