Variant 17-64859995-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000584306.6(LRRC37A3):c.4151A>G(p.Glu1384Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,732 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LRRC37A3
ENST00000584306.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.741

Variant links:

Genes affected

LRRC37A3 (HGNC:32427): (leucine rich repeat containing 37 member A3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A3 links:

LOC105376844 (HGNC:):

LOC105376844 links:

Genome browser will be placed here

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=0.043711275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A3	NM_199340.5 linkuse as main transcript	c.4151A>G	p.Glu1384Gly	missense_variant	12/15	ENST00000584306.6	NP_955372.2	O60309
LRRC37A3	NM_001303255.3 linkuse as main transcript	c.1505A>G	p.Glu502Gly	missense_variant	8/11		NP_001290184.1	J3QTJ5
LOC105376844	XR_934912.4 linkuse as main transcript	n.177+10008T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37A3	ENST00000584306.6 linkuse as main transcript	c.4151A>G	p.Glu1384Gly	missense_variant	12/15	1	NM_199340.5	ENSP00000464535.1		O60309

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247758

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.000336

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461410

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000414

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

Jan 23, 2024

The c.4151A>G (p.E1384G) alteration is located in exon 11 (coding exon 9) of the LRRC37A3 gene. This alteration results from a A to G substitution at nucleotide position 4151, causing the glutamic acid (E) at amino acid position 1384 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

.;T;.;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.54

T;T;T;T;.

M_CAP

Benign

0.058

MetaRNN

Benign

0.044

T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.5

.;.;.;M;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-4.0

.;D;D;D;.

REVEL

Benign

0.036

Sift

Benign

0.095

.;T;T;T;.

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

0.22

.;.;.;B;B

Vest4

0.093

MVP

0.16

ClinPred

0.058

GERP RS

2.4

Varity_R

0.066

gMVP

0.21

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