Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_016648.4(LARP7):c.213_214dupAT(p.Ser72TyrfsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

LARP7
NM_016648.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.65

Publications

3 publications found

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:

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

MIR302CHG links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-112646356-G-GAT is Pathogenic according to our data. Variant chr4-112646356-G-GAT is described in ClinVar as Pathogenic. ClinVar VariationId is 374899.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LARP7	NM_016648.4	MANE Select	c.213_214dupAT	p.Ser72TyrfsTer10	frameshift	Exon 3 of 13	NP_057732.2
LARP7	NM_001370974.1		c.213_214dupAT	p.Ser72TyrfsTer10	frameshift	Exon 3 of 13	NP_001357903.1
LARP7	NM_001370975.1		c.213_214dupAT	p.Ser72TyrfsTer10	frameshift	Exon 3 of 13	NP_001357904.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LARP7	ENST00000344442.10	TSL:2 MANE Select	c.213_214dupAT	p.Ser72TyrfsTer10	frameshift	Exon 3 of 13	ENSP00000344950.5
LARP7	ENST00000509061.5	TSL:1	c.213_214dupAT	p.Ser72TyrfsTer10	frameshift	Exon 5 of 15	ENSP00000422626.2
LARP7	ENST00000509622.5	TSL:1	n.110_111dupAT		non_coding_transcript_exon	Exon 3 of 13	ENSP00000422451.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcephalic primordial dwarfism, Alazami type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.7

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

Splicing

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

Publications

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4-112646356-GAT-GATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over