Variant 4-112644863-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016648.4(LARP7):c.194G>A(p.Arg65Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,415,506 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LARP7
NM_016648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

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:

LARP7 (HGNC:):

LARP7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20635659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP7	NM_016648.4 linkuse as main transcript	c.194G>A	p.Arg65Lys	missense_variant	2/13	ENST00000344442.10	NP_057732.2	Q4G0J3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP7	ENST00000344442.10 linkuse as main transcript	c.194G>A	p.Arg65Lys	missense_variant	2/13	2	NM_016648.4	ENSP00000344950.5		Q4G0J3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231352

Hom.:

AF XY:

0.00000795

AC XY:

AN XY:

125800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1415506

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 20, 2021

This variant is present in population databases (rs780254262, ExAC 0.009%). This sequence change replaces arginine with lysine at codon 65 of the LARP7 protein (p.Arg65Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. This variant has not been reported in the literature in individuals affected with LARP7-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

.;.;T;T;.;T

Eigen

Benign

-0.011

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.88

.;D;T;D;D;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.21

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;.;.;.;N;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.44

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.069

T;T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T;T

Polyphen

0.98

D;.;.;B;D;.

Vest4

0.33

MutPred

0.46

Gain of ubiquitination at R65 (P = 0.0162);.;Gain of ubiquitination at R65 (P = 0.0162);Gain of ubiquitination at R65 (P = 0.0162);Gain of ubiquitination at R65 (P = 0.0162);Gain of ubiquitination at R65 (P = 0.0162);

MVP

0.38

MPC

0.071

ClinPred

0.39

GERP RS

4.9

Varity_R

0.37

gMVP

0.23

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over