rs1554011754

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_016648.4(LARP7):c.802_1142+267del variant causes a exon loss change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LARP7
NM_016648.4 exon_loss

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

LARP7 (HGNC:24912): (La ribonucleoprotein 7, transcriptional regulator) This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

LARP7 links:

MIR302D (HGNC:31765): (microRNA 302d) 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]

MIR302D links:

MIR367 (HGNC:31781): (microRNA 367) 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]

MIR367 links:

MIR302CHG (HGNC:41070): (miR-302/367 cluster host gene)

MIR302CHG links:

MIR302A (HGNC:31623): (microRNA 302a) 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]

MIR302A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-112647351-GAACCCCAAAAGCAGTGCTCAAAGAAAAAGAAAAAACGGGACAGAGTTGAAGCATCTAGCTTACCTGAAGTCAGAACAGGGAAGAGGAAGAGAAGCAGCTCTGAAGATGCAGAATCCCTAGCTCCCCGATCAAAAGTAAAGAAAATTATTCAGAAAGACATCATTAAGGAAGCATCAGAAGCTTCCAAGGAAAATAGAGGTAAAACTACAAGGTTTTAATTAGATAAAACTAATTAATTTTAATTAATTAGTTTTTAATTAATTAGGTTTTAATTGGCTTCTGTTTCACCCATTTCACAGCCCCATGTCTTAACGGAGAGCTTTTTTATTTATTTCAAGATATAGAAATCTCTACTGAAGAGGAAAAGGATACTGGAGATCTAAAAGATAGCTCTCTCTTGAAAACAAAAAGGAAACATAAGAAAAAACATAAAGAGAGACATAAAATGGGAGAAGAAGTTATACCATTAAGAGTGCTATCAAAGTAAGTCTGTGGTTTAAATTCTGTCATTGGCTTAACAATCCATCACCATTGCTAAAGTGCAATTCCAATTTATATTCAACAGAGTTGCATATTAGCAACAGTAATGGCCTGTAGCCAAGAACTGCACACAGTGTGGGCGTTAACGCAATTGCTGATTAGGTAGGAACCACCACACTCAAACATGGAAGCACTTATTTTTGTCATGTCACAGCAAGTGCCTCCATGTTAAAGTAGAGGGGGCCCCTTAACAGATGTAAAAATACAA-G is Pathogenic according to our data. Variant chr4-112647351-GAACCCCAAAAGCAGTGCTCAAAGAAAAAGAAAAAACGGGACAGAGTTGAAGCATCTAGCTTACCTGAAGTCAGAACAGGGAAGAGGAAGAGAAGCAGCTCTGAAGATGCAGAATCCCTAGCTCCCCGATCAAAAGTAAAGAAAATTATTCAGAAAGACATCATTAAGGAAGCATCAGAAGCTTCCAAGGAAAATAGAGGTAAAACTACAAGGTTTTAATTAGATAAAACTAATTAATTTTAATTAATTAGTTTTTAATTAATTAGGTTTTAATTGGCTTCTGTTTCACCCATTTCACAGCCCCATGTCTTAACGGAGAGCTTTTTTATTTATTTCAAGATATAGAAATCTCTACTGAAGAGGAAAAGGATACTGGAGATCTAAAAGATAGCTCTCTCTTGAAAACAAAAAGGAAACATAAGAAAAAACATAAAGAGAGACATAAAATGGGAGAAGAAGTTATACCATTAAGAGTGCTATCAAAGTAAGTCTGTGGTTTAAATTCTGTCATTGGCTTAACAATCCATCACCATTGCTAAAGTGCAATTCCAATTTATATTCAACAGAGTTGCATATTAGCAACAGTAATGGCCTGTAGCCAAGAACTGCACACAGTGTGGGCGTTAACGCAATTGCTGATTAGGTAGGAACCACCACACTCAAACATGGAAGCACTTATTTTTGTCATGTCACAGCAAGTGCCTCCATGTTAAAGTAGAGGGGGCCCCTTAACAGATGTAAAAATACAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 211371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP7	NM_016648.4 link	c.802_1142+267del		exon_loss_variant	Exon 8 of 13	ENST00000344442.10	NP_057732.2	Q4G0J3-1
LARP7	NM_016648.4 link	c.802_1142+267del	p.Pro268AspfsTer42	frameshift_variant	Exon 7 of 13	ENST00000344442.10	NP_057732.2	Q4G0J3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP7	ENST00000344442.10 link	c.802_1142+267del		exon_loss_variant	Exon 8 of 13	2	NM_016648.4	ENSP00000344950.5		Q4G0J3-1
LARP7	ENST00000344442.10 link	c.802_1142+267del	p.Pro268AspfsTer42	frameshift_variant	Exon 8 of 13	2	NM_016648.4	ENSP00000344950.5		Q4G0J3-1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcephalic primordial dwarfism, Alazami type

Pathogenic:1

Jul 02, 2015

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.