17-46515041-C-T

Variant names:

• chr17-46515041-C-T
• rs550252059
• NM_001006607.3:c.2329C>T

Variant summary

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

The NM_001006607.3(LRRC37A2):​c.2329C>T​(p.Pro777Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P777T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 6)
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07005662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37A2	NM_001006607.3	c.2329C>T	p.Pro777Ser	missense_variant	Exon 1 of 14	ENST00000576629.6	NP_001006608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC37A2	ENST00000576629.6	c.2329C>T	p.Pro777Ser	missense_variant	Exon 1 of 14	5	NM_001006607.3	ENSP00000459551.1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.4
DANN	Benign	0.83
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.5	.;D
REVEL	Benign	0.046
Sift	Benign	0.044	.;D
Sift4G	Benign	0.20	T;T
Polyphen		0.0040	B;B
Vest4		0.20
MutPred		0.23		Gain of phosphorylation at P777 (P = 0.0187);Gain of phosphorylation at P777 (P = 0.0187);
MVP		0.030
ClinPred		0.059	T
GERP RS		-1.8
Varity_R		0.062
gMVP		0.11

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

Other links and lift over

dbSNP: rs550252059; hg19: chr17-44592407;