Variant 3-169800667-T-G 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_001172779.2(LRRC34):c.745A>C(p.Ser249Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,527,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

LRRC34
NM_001172779.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

LRRC34 (HGNC:28408): (leucine rich repeat containing 34) Predicted to be involved in cell differentiation. Predicted to be located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LRRC34 links:

LRRC34 (HGNC:):

LRRC34 links:

Genome browser will be placed here

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=0.092829436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC34	NM_001172779.2 linkuse as main transcript	c.745A>C	p.Ser249Arg	missense_variant	7/11	ENST00000446859.7	NP_001166250.1	Q8IZ02-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC34	ENST00000446859.7 linkuse as main transcript	c.745A>C	p.Ser249Arg	missense_variant	7/11	2	NM_001172779.2	ENSP00000414635.1		Q8IZ02-2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

132890

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

72330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000832

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:

0.000421

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000433

AC:

595

AN:

1375412

Hom.:

Cov.:

AF XY:

0.000455

AC XY:

309

AN XY:

679158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000850

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:

0.000537

Gnomad4 OTH exome

AF:

0.000278

GnomAD4 genome

AF:

0.000178

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000407

Hom.:

10794

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000669

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0018

T;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.75

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.051

Sift

Benign

0.033

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.71

.;P

Vest4

0.26

MutPred

0.27

.;Gain of catalytic residue at S188 (P = 0.0484);

MVP

0.46

MPC

0.24

ClinPred

0.19

GERP RS

3.4

Varity_R

0.23

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over