Variant 4-112644860-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016648.4(LARP7):c.191C>A(p.Ser64Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,418,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LARP7
NM_016648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP7	NM_016648.4 linkuse as main transcript	c.191C>A	p.Ser64Tyr	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.191C>A	p.Ser64Tyr	missense_variant	2/13	2	NM_016648.4	ENSP00000344950.5		Q4G0J3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232194

Hom.:

AF XY:

0.0000238

AC XY:

AN XY:

126232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000124

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:

0.00000211

AC:

AN:

1418626

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

705310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000240

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000527

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with LARP7-related conditions. This variant is present in population databases (rs758628046, ExAC 0.009%). This sequence change replaces serine with tyrosine at codon 64 of the LARP7 protein (p.Ser64Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

.;.;T;T;.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.61

D;D;D;D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.8

M;.;.;.;M;.

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0050

D;D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;.

Vest4

0.83

MutPred

0.50

Loss of disorder (P = 0.0135);.;Loss of disorder (P = 0.0135);Loss of disorder (P = 0.0135);Loss of disorder (P = 0.0135);Loss of disorder (P = 0.0135);

MVP

0.76

MPC

0.33

ClinPred

0.84

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.67

gMVP

0.56

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