Variant chr17-46514949-C-G 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_001006607.3(LRRC37A2):c.2237C>G(p.Thr746Ser) 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: not found (cov: 7)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A2
NM_001006607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0750

Variant links:

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) 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]

ARL17A links:

ARL17A (HGNC:):

ARL17A 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=0.05551368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A2	NM_001006607.3 linkuse as main transcript	c.2237C>G	p.Thr746Ser	missense_variant	1/14	ENST00000576629.6	NP_001006608.2	A6NM11Q5YKG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37A2	ENST00000576629.6 linkuse as main transcript	c.2237C>G	p.Thr746Ser	missense_variant	1/14	5	NM_001006607.3	ENSP00000459551.1		A6NM11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000759

AC:

AN:

131762

Hom.:

AF XY:

0.0000145

AC XY:

AN XY:

68834

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000434

AC:

AN:

690636

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

340762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000405

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000143

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

May 26, 2024

The c.2237C>G (p.T746S) alteration is located in exon 1 (coding exon 1) of the LRRC37A2 gene. This alteration results from a C to G substitution at nucleotide position 2237, causing the threonine (T) at amino acid position 746 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.7

DANN

Benign

0.75

DEOGEN2

Benign

0.0041

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.39

.;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.14

Sift

Benign

0.42

.;T

Sift4G

Benign

0.29

T;T

Polyphen

0.073

B;B

Vest4

0.24

MutPred

0.14

Loss of glycosylation at T746 (P = 0.0784);Loss of glycosylation at T746 (P = 0.0784);

MVP

0.048

ClinPred

0.041

GERP RS

-1.5

Varity_R

0.064

gMVP

0.044

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