17-32021732-C-G

Position:

• chr17-32021732-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321350.2(LRRC37B):​c.340C>G​(p.Leu114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC37B NM_001321350.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.578

Genes affected

LRRC37B (HGNC:29070): (leucine rich repeat containing 37B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09175429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37B	NM_001321350.2	c.340C>G	p.Leu114Val	missense_variant	4/15	ENST00000543378.7
LRRC37B	NM_052888.3	c.586C>G	p.Leu196Val	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37B	ENST00000543378.7	c.340C>G	p.Leu114Val	missense_variant	4/15	2	NM_001321350.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.586C>G (p.L196V) alteration is located in exon 1 (coding exon 1) of the LRRC37B gene. This alteration results from a C to G substitution at nucleotide position 586, causing the leucine (L) at amino acid position 196 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T;T;.;T;T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.56	T;T;T;T;T;T;.
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.092	T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.8	.;.;.;.;.;L;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.87	.;.;N;N;.;N;N
REVEL	Benign	0.061
Sift	Benign	0.049	.;.;D;D;.;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T
Polyphen		1.0	.;.;.;.;.;D;D
Vest4		0.050, 0.017, 0.049, 0.029, 0.025
MutPred		0.16		.;.;.;.;.;Gain of MoRF binding (P = 0.0755);Gain of MoRF binding (P = 0.0755);
MVP		0.13
MPC		0.25
ClinPred		0.074	T
GERP RS		-0.41
Varity_R		0.047
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: chr17-30348751;