rs202103242

Variant names:

• chr17-30118090-A-G
• rs202103242
• NM_032141.4:c.31A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-30118090-A-G
• chr17-30118090-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032141.4(NSRP1):​c.31A>G​(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,602 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NSRP1 NM_032141.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 0 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, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ENSG00000265394 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35710603).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032141.4. 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
	NSRP1	NM_032141.4	MANE Select	c.31A>G	p.Ile11Val	missense	Exon 2 of 7	NP_115517.1	Q9H0G5
	NSRP1	NM_001261467.2		c.-49+1227A>G		intron	N/A	NP_001248396.1	A0A024QZ33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	ENST00000247026.10	TSL:1 MANE Select	c.31A>G	p.Ile11Val	missense	Exon 2 of 7	ENSP00000247026.5	Q9H0G5
	NSRP1	ENST00000612959.4	TSL:1	c.-49+1227A>G		intron	N/A	ENSP00000477862.1	A0A024QZ33
	NSRP1	ENST00000475652.5	TSL:1	n.62A>G		non_coding_transcript_exon	Exon 3 of 8	ENSP00000464569.1	J3QS82

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251298 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461422 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727036

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111736

Other (OTH) AF: 0.0000497 AC: 3 AN: 60362

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000506 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000659 AC: 8

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.24
Sift	Uncertain	0.022	D
Sift4G	Benign	0.28	T
Polyphen		0.99	D
Vest4		0.38
MVP		0.76
MPC		0.19
ClinPred		0.33	T
GERP RS		5.5
PromoterAI		0.026	Neutral
Varity_R		0.17
gMVP		0.21

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: rs202103242; hg19: chr17-28445108;