Variant 17-46297322-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014834.4(LRRC37A):c.2189A>T(p.Lys730Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 14)

Exomes 𝑓: 0.000023 ( 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: -1.27

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10527086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A	NM_014834.4 linkuse as main transcript	c.2189A>T	p.Lys730Ile	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.2189A>T	p.Lys730Ile	missense_variant	1/14	1	NM_014834.4	ENSP00000326324	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

107276

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000313

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:

0.0000386

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000233

AC:

AN:

942210

Hom.:

Cov.:

AF XY:

0.0000329

AC XY:

AN XY:

485586

show subpopulations

Gnomad4 AFR exome

AF:

0.0000424

Gnomad4 AMR exome

AF:

0.0000367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000289

Gnomad4 FIN exome

AF:

0.0000228

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000238

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000280

AC:

AN:

107276

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

50386

show subpopulations

Gnomad4 AFR

AF:

0.0000313

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:

0.0000386

Gnomad4 OTH

AF:

0.00

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 14, 2022

The c.2189A>T (p.K730I) alteration is located in exon 1 (coding exon 1) of the LRRC37A gene. This alteration results from a A to T substitution at nucleotide position 2189, causing the lysine (K) at amino acid position 730 to be replaced by an isoleucine (I). 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

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.7

DANN

Benign

0.87

DEOGEN2

Benign

0.077

.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.046

Sift

Benign

0.083

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.79

.;P

Vest4

0.17

MutPred

0.33

Loss of ubiquitination at K730 (P = 0.0019);Loss of ubiquitination at K730 (P = 0.0019);

MVP

0.043

ClinPred

0.30

GERP RS

0.86

Varity_R

0.31

gMVP

0.077

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