17-46297513-C-T

Variant names:

• chr17-46297513-C-T
• NM_014834.4:c.2380C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

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]

ACMG classification

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
LRRC37A	NM_014834.4	c.2380C>T	p.Pro794Ser	missense_variant	Exon 1 of 14	ENST00000320254.5	NP_055649.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC37A	ENST00000320254.5	c.2380C>T	p.Pro794Ser	missense_variant	Exon 1 of 14	1	NM_014834.4	ENSP00000326324.5

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

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;