17-46297513-C-T

Variant summary

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

The NM_014834.4(LRRC37A):​c.2380C>T​(p.Pro794Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P794L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 8)

Consequence

LRRC37A
NM_014834.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0960
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10217479).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC37ANM_014834.4 linkc.2380C>T p.Pro794Ser missense_variant Exon 1 of 14 ENST00000320254.5 NP_055649.4 A6NMS7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC37AENST00000320254.5 linkc.2380C>T p.Pro794Ser missense_variant Exon 1 of 14 1 NM_014834.4 ENSP00000326324.5 A6NMS7

Frequencies

GnomAD3 genomes
Cov.:
8
GnomAD4 exome
Cov.:
7
GnomAD4 genome
Cov.:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2380C>T (p.P794S) alteration is located in exon 1 (coding exon 1) of the LRRC37A gene. This alteration results from a C to T substitution at nucleotide position 2380, causing the proline (P) at amino acid position 794 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
0.098
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.78
DANN
Uncertain
0.99
DEOGEN2
Benign
0.083
.;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.0
.;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.054
Sift
Uncertain
0.010
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
0.20
.;B
Vest4
0.11
MutPred
0.20
Loss of catalytic residue at P793 (P = 0.0131);Loss of catalytic residue at P793 (P = 0.0131);
MVP
0.043
ClinPred
0.42
T
GERP RS
2.0
Varity_R
0.090
gMVP
0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-44374879; API