17-30116854-C-G

Variant summary

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

The NM_032141.4(NSRP1):c.11C>G(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P4S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NSRP1 NM_032141.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

Genes affected

NSRP1 (HGNC:25305): (nuclear speckle splicing regulatory protein 1) Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSRP1	NM_032141.4	c.11C>G	p.Pro4Arg	missense_variant	1/7	ENST00000247026.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSRP1	ENST00000247026.10	c.11C>G	p.Pro4Arg	missense_variant	1/7	1	NM_032141.4	P4
	ENST00000582938.1	n.106+538G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.11C>G (p.P4R) alteration is located in exon 1 (coding exon 1) of the NSRP1 gene. This alteration results from a C to G substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
Cadd	Pathogenic	33
Dann	Benign	0.97
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.74	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	0.97	D;D;N
PrimateAI	Uncertain	0.73	T
Sift4G	Pathogenic	0.0	D;T;.
Polyphen		1.0	.;D;.
Vest4		0.62
MutPred		0.46		Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);
MVP		0.55
MPC		0.29
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.31
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-28443872;