17-46514949-C-G

Variant names:

• chr17-46514949-C-G
• rs755924095
• NM_001006607.3:c.2237C>G

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05551368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37A2	NM_001006607.3	c.2237C>G	p.Thr746Ser	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.2237C>G	p.Thr746Ser	missense_variant	Exon 1 of 14	5	NM_001006607.3	ENSP00000459551.1

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD3 exomes AF: 0.00000759 AC: 1 AN: 131762 Hom.: 0 AF XY: 0.0000145 AC XY: 1 AN XY: 68834

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: 3 AN: 690636 Hom.: 0 Cov.: 5 AF XY: 0.00000293 AC XY: 1 AN XY: 340762

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.: 7

ExAC AF: 0.0000143 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
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	N
LIST_S2	Benign	0.39	.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.60	T
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	T
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

Other links and lift over

dbSNP: rs755924095; hg19: chr17-44592315;