Variant 17-64860035-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_199340.5(LRRC37A3):c.4111C>T(p.Pro1371Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,613,886 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P1371P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.015 ( 51 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 50 hom. )

Consequence

LRRC37A3
NM_199340.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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 Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, LRRC37A3

BP4

Computational evidence support a benign effect (MetaRNN=0.0026704073).

BP6

Variant 17-64860035-G-A is Benign according to our data. Variant chr17-64860035-G-A is described in ClinVar as [Benign]. Clinvar id is 768910.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRC37A3	NM_199340.5 linkuse as main transcript	c.4111C>T	p.Pro1371Ser	missense_variant	12/15	ENST00000584306.6
LOC105376844	XR_934912.4 linkuse as main transcript	n.177+10048G>A		intron_variant, non_coding_transcript_variant
LRRC37A3	NM_001303255.3 linkuse as main transcript	c.1465C>T	p.Pro489Ser	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A3	ENST00000584306.6 linkuse as main transcript	c.4111C>T	p.Pro1371Ser	missense_variant	12/15	1	NM_199340.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2221

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

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:

0.000118

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.00387

AC:

962

AN:

248872

Hom.:

AF XY:

0.00291

AC XY:

393

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.0556

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00153

AC:

2238

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

924

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0546

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.0146

AC:

2224

AN:

152234

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1050

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0502

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.0170

ExAC

AF:

0.00491

AC:

595

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

Cadd

Benign

1.5

Dann

Uncertain

0.99

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.63

T;T;T;T;.

MetaRNN

Benign

0.0027

T;T;T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

REVEL

Benign

0.067

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.90

.;.;.;P;P

Vest4

0.15

MVP

0.081

ClinPred

0.063

GERP RS

-0.21

Varity_R

0.099

gMVP

0.31

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