Variant chr17-46322338-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_014834.4(LRRC37A):c.2923C>A(p.Pro975Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 10)

Exomes 𝑓: 0.0000028 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A
NM_014834.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31785297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A	NM_014834.4 linkuse as main transcript	c.2923C>A	p.Pro975Thr	missense_variant	6/14	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.2923C>A	p.Pro975Thr	missense_variant	6/14	1	NM_014834.4	ENSP00000326324	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000182

AC:

AN:

109838

Hom.:

AF XY:

0.0000346

AC XY:

AN XY:

57790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000120

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000278

AC:

AN:

718890

Hom.:

Cov.:

AF XY:

0.00000567

AC XY:

AN XY:

352556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000764

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000295

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

Oct 05, 2021

The c.2923C>A (p.P975T) alteration is located in exon 6 (coding exon 6) of the LRRC37A gene. This alteration results from a C to A substitution at nucleotide position 2923, causing the proline (P) at amino acid position 975 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.0

.;.;M

MutationTaster

Benign

1.0

D;D;N;N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.9

D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0040

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.44

.;.;B

Vest4

0.61

MutPred

0.52

.;Gain of catalytic residue at P975 (P = 0.1137);Gain of catalytic residue at P975 (P = 0.1137);

MVP

0.043

ClinPred

0.83

GERP RS

2.4

Varity_R

0.39

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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