Variant 8-85109629-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033402.5(LRRCC1):c.139G>T(p.Ala47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,609,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

LRRCC1
NM_033402.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

LRRCC1 (HGNC:29373): (leucine rich repeat and coiled-coil centrosomal protein 1) This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome. [provided by RefSeq, Mar 2017]

LRRCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03805399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRCC1	NM_033402.5 linkuse as main transcript	c.139G>T	p.Ala47Ser	missense_variant	2/19	ENST00000360375.8	NP_208325.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRCC1	ENST00000360375.8 linkuse as main transcript	c.139G>T	p.Ala47Ser	missense_variant	2/19	1	NM_033402.5	ENSP00000353538	P2	Q9C099-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246864

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000391

AC:

AN:

1457590

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

725202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000460

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.139G>T (p.A47S) alteration is located in exon 2 (coding exon 2) of the LRRCC1 gene. This alteration results from a G to T substitution at nucleotide position 139, causing the alanine (A) at amino acid position 47 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.00067

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.081

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

B;P

Vest4

0.16

MVP

0.12

MPC

0.067

ClinPred

0.058

GERP RS

1.0

Varity_R

0.039

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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