rs749063424

Variant names:

• chr10-133423299-C-G
• rs749063424
• NM_001391974.1:c.383G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-133423299-C-G
• chr10-133423299-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001391974.1(SPRN):​c.383G>C​(p.Gly128Ala) 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. 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. G128E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRN NM_001391974.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10582298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRN	NM_001391974.1	c.383G>C	p.Gly128Ala	missense_variant	Exon 2 of 2	ENST00000685335.1	NP_001378903.1
SPRN	NM_001012508.6	c.383G>C	p.Gly128Ala	missense_variant	Exon 2 of 2		NP_001012526.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRN	ENST00000685335.1	c.383G>C	p.Gly128Ala	missense_variant	Exon 2 of 2		NM_001391974.1	ENSP00000510252.1
SPRN	ENST00000414069.2	c.383G>C	p.Gly128Ala	missense_variant	Exon 2 of 2	1		ENSP00000433712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.019
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.28	T
Polyphen		0.22	B
Vest4		0.21
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0275);
MVP		0.040
ClinPred		0.13	T
GERP RS		1.8
Varity_R		0.14
gMVP		0.079

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

Other links and lift over

dbSNP: rs749063424; hg19: chr10-135236803;