chr17-46514949-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006607.3(LRRC37A2):​c.2237C>T​(p.Thr746Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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. T746S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 7)
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12923375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A2	NM_001006607.3	MANE Select	c.2237C>T	p.Thr746Ile	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.2237C>T	p.Thr746Ile	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*21+2145G>A		intron	N/A	NP_001275741.1	Q8IVW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A2	ENST00000576629.6	TSL:5 MANE Select	c.2237C>T	p.Thr746Ile	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.2237C>T	p.Thr746Ile	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-88-2413C>T		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.2
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.075
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.031	D
Polyphen		0.91	P
Vest4		0.15
MutPred		0.20		Loss of glycosylation at T746 (P = 0.0043)
MVP		0.072
ClinPred		0.32	T
GERP RS		-1.5
Varity_R		0.081
gMVP		0.070

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

Other links and lift over

dbSNP: rs755924095; hg19: chr17-44592315;