Variant chr17-46297453-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014834.4(LRRC37A):c.2320G>A(p.Ala774Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A
NM_014834.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.60

Variant links:

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A links:

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058970273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A	NM_014834.4 linkuse as main transcript	c.2320G>A	p.Ala774Thr	missense_variant	1/14	ENST00000320254.5	NP_055649.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37A	ENST00000320254.5 linkuse as main transcript	c.2320G>A	p.Ala774Thr	missense_variant	1/14	1	NM_014834.4	ENSP00000326324	P2

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

126366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000876

Gnomad ASJ

AF:

0.00321

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000219

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000226

AC:

288

AN:

1272810

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

146

AN XY:

639402

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.00247

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.0000429

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000300

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000198

AC:

AN:

126366

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

60220

show subpopulations

Gnomad4 AFR

AF:

0.0000271

Gnomad4 AMR

AF:

0.0000876

Gnomad4 ASJ

AF:

0.00321

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000219

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000247

Hom.:

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

Apr 28, 2022

The c.2320G>A (p.A774T) alteration is located in exon 1 (coding exon 1) of the LRRC37A gene. This alteration results from a G to A substitution at nucleotide position 2320, causing the alanine (A) at amino acid position 774 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.7

DANN

Benign

0.58

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.078

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.98

.;D

Vest4

0.13

MVP

0.043

ClinPred

0.12

GERP RS

-0.34

Varity_R

0.085

gMVP

0.054

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