17-30184960-G-C

Variant names:

• chr17-30184960-G-C
• rs1979572
• NM_032141.4:c.963G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032141.4(NSRP1):​c.963G>C​(p.Gln321His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NSRP1 NM_032141.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 31 publications found

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]

NSRP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity, seizures, and brain abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064548165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSRP1	NM_032141.4	c.963G>C	p.Gln321His	missense_variant	Exon 7 of 7	ENST00000247026.10	NP_115517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSRP1	ENST00000247026.10	c.963G>C	p.Gln321His	missense_variant	Exon 7 of 7	1	NM_032141.4	ENSP00000247026.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.2
DANN	Benign	0.96
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		-0.42
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.78	N;.
REVEL	Benign	0.083
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.17	T;T
Polyphen		0.85	P;.
Vest4		0.093
MutPred		0.13		Loss of solvent accessibility (P = 0.0576);.;
MVP		0.26
MPC		0.086
ClinPred		0.14	T
GERP RS		2.0
Varity_R		0.079
gMVP		0.016

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: rs1979572; hg19: chr17-28511978;