17-30117165-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_032141.4(NSRP1):c.20+302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 708,838 control chromosomes in the GnomAD database, including 84,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14884 hom., cov: 31)
  • Exomes 𝑓: 0.49 (69874 hom.)
• Consequence: NSRP1 NM_032141.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.939

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]

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]

hsa-mir-423 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-30117165-A-C is Benign according to our data. Variant chr17-30117165-A-C is described in ClinVar as [Benign]. Clinvar id is 1221211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSRP1	NM_032141.4	c.20+302A>C		intron_variant		ENST00000247026.10
MIR423	NR_029945.1	n.87A>C		non_coding_transcript_exon_variant	1/1
MIR3184	NR_036149.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSRP1	ENST00000247026.10	c.20+302A>C		intron_variant		1	NM_032141.4	P4
MIR423	ENST00000362201.2	n.87A>C		non_coding_transcript_exon_variant	1/1
hsa-mir-423	ENST00000586878.1	n.8T>G		non_coding_transcript_exon_variant	1/1
	ENST00000582938.1	n.106+227T>G		intron_variant, non_coding_transcript_variant		3
MIR3184	ENST00000637796.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64399 AN: 151734 Hom.: 14886 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.500 AC: 80035 AN: 159944 Hom.: 20940 AF XY: 0.504 AC XY: 43008 AN XY: 85382

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.538

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.490 AC: 272803 AN: 556986 Hom.: 69874 Cov.: 2 AF XY: 0.493 AC XY: 148252 AN XY: 300794

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.424 AC: 64399 AN: 151852 Hom.: 14884 Cov.: 31 AF XY: 0.432 AC XY: 32082 AN XY: 74178

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.465

Alfa AF: 0.455 Hom.: 16721

Bravo AF: 0.427

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

This variant is associated with the following publications: (PMID: 22593246, 19950226) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	19
Dann	Benign	0.82

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: rs6505162; hg19: chr17-28444183; COSMIC: COSV55936190; COSMIC: COSV55936190;