17-30116853-C-G

Variant names:

• chr17-30116853-C-G
• rs761196282
• ENST00000612959.4:c.-59C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001261467.2(NSRP1):​c.-59C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,423,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 0.0000035 (1 hom.)
• Consequence: NSRP1 NM_001261467.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• 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]

ENSG00000265394 (HGNC:):

MIR423 (HGNC:31880): (microRNA 423) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3184 (HGNC:38182): (microRNA 3184) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19883373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261467.2. 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.10C>G	p.Pro4Ala	missense	Exon 1 of 7	NP_115517.1	Q9H0G5
	NSRP1	NM_001261467.2		c.-59C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001248396.1	A0A024QZ33
	NSRP1	NM_001261467.2		c.-59C>G		5_prime_UTR	Exon 1 of 6	NP_001248396.1	A0A024QZ33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	ENST00000612959.4	TSL:1	c.-59C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000477862.1	A0A024QZ33
	NSRP1	ENST00000247026.10	TSL:1 MANE Select	c.10C>G	p.Pro4Ala	missense	Exon 1 of 7	ENSP00000247026.5	Q9H0G5
	NSRP1	ENST00000612959.4	TSL:1	c.-59C>G		5_prime_UTR	Exon 1 of 6	ENSP00000477862.1	A0A024QZ33

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000351 AC: 5 AN: 1423834 Hom.: 1 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704414

African (AFR) AF: 0.00 AC: 0 AN: 32750

American (AMR) AF: 0.00 AC: 0 AN: 38684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.0000527 AC: 2 AN: 37928

South Asian (SAS) AF: 0.00 AC: 0 AN: 81070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1092350

Other (OTH) AF: 0.00 AC: 0 AN: 59028

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Benign	0.89
DEOGEN2	Benign	0.052	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.058
Sift	Benign	0.38	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.69	P
Vest4		0.48
MutPred		0.38		Gain of MoRF binding (P = 0.0345)
MVP		0.48
MPC		0.16
ClinPred		0.48	T
GERP RS		4.3
PromoterAI		-0.080	Neutral
Varity_R		0.17
gMVP		0.25
Mutation Taster		=86/14	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: rs761196282; hg19: chr17-28443871;