17-64859594-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_199340.5(LRRC37A3):c.4552G>A(p.Val1518Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,612,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

LRRC37A3
NM_199340.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.555

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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, LRRC37A3

BP4

Computational evidence support a benign effect (MetaRNN=0.014185905).

BP6

Variant 17-64859594-C-T is Benign according to our data. Variant chr17-64859594-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2356613.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRC37A3	NM_199340.5 linkuse as main transcript	c.4552G>A	p.Val1518Ile	missense_variant	12/15	ENST00000584306.6
LOC105376844	XR_934912.4 linkuse as main transcript	n.177+9607C>T		intron_variant, non_coding_transcript_variant
LRRC37A3	NM_001303255.3 linkuse as main transcript	c.1906G>A	p.Val636Ile	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A3	ENST00000584306.6 linkuse as main transcript	c.4552G>A	p.Val1518Ile	missense_variant	12/15	1	NM_199340.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

151070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000286

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000994

AC:

AN:

251406

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000232

AC:

AN:

151070

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73654

show subpopulations

Gnomad4 AFR

AF:

0.000487

Gnomad4 AMR

AF:

0.0000666

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000286

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000337

Hom.:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

Cadd

Benign

2.1

Dann

Benign

0.13

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.34

T;T;T;T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.014

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.85

REVEL

Benign

0.051

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;B;.

Vest4

0.12

MutPred

0.23

.;.;.;Loss of MoRF binding (P = 0.1266);Loss of MoRF binding (P = 0.1266);.;

MVP

0.014

ClinPred

0.0097

GERP RS

-2.0

Varity_R

0.018

gMVP

0.024

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