Variant 17-64859581-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_199340.5(LRRC37A3):c.4565G>A(p.Gly1522Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LRRC37A3
NM_199340.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, LRRC37A3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRC37A3	NM_199340.5 linkuse as main transcript	c.4565G>A	p.Gly1522Asp	missense_variant	12/15	ENST00000584306.6
LOC105376844	XR_934912.4 linkuse as main transcript	n.177+9594C>T		intron_variant, non_coding_transcript_variant
LRRC37A3	NM_001303255.3 linkuse as main transcript	c.1919G>A	p.Gly640Asp	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A3	ENST00000584306.6 linkuse as main transcript	c.4565G>A	p.Gly1522Asp	missense_variant	12/15	1	NM_199340.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

150892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000220

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251294

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000124

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:

0.0000144

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000596

AC:

AN:

150892

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

73564

show subpopulations

Gnomad4 AFR

AF:

0.000220

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Sep 27, 2022

The c.4565G>A (p.G1522D) alteration is located in exon 11 (coding exon 9) of the LRRC37A3 gene. This alteration results from a G to A substitution at nucleotide position 4565, causing the glycine (G) at amino acid position 1522 to be replaced by an aspartic acid (D). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.80

T;T;T;T;.;T

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.54

D;D;D;D;D;D

MetaSVM

Benign

-0.82

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.84

REVEL

Benign

0.19

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

.;.;.;D;D;.

Vest4

0.33

MVP

0.23

ClinPred

0.80

GERP RS

1.4

Varity_R

0.53

gMVP

0.42

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