17-32021237-G-T

Position:

• chr17-32021237-G-T

Variant summary

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

The ENST00000341671.12(LRRC37B):​c.91G>T​(p.Val31Phe) 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 ENST00000341671.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01

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=0.10118815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37B	NM_001321350.2	c.1-156G>T		intron_variant		ENST00000543378.7
LRRC37B	NM_052888.3	c.91G>T	p.Val31Phe	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37B	ENST00000543378.7	c.1-156G>T		intron_variant		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

Mar 19, 2024

The c.91G>T (p.V31F) alteration is located in exon 1 (coding exon 1) of the LRRC37B gene. This alteration results from a G to T substitution at nucleotide position 91, causing the valine (V) at amino acid position 31 to be replaced by a phenylalanine (F). 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	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	.;T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.77	T;T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.0	.;.;M;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N;.;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.0070	D;.;D;D
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.98	.;.;D;D
Vest4		0.071
MutPred		0.23		.;.;Loss of ubiquitination at K32 (P = 0.1322);Loss of ubiquitination at K32 (P = 0.1322);
MVP		0.18
MPC		0.35
ClinPred		0.43	T
GERP RS		0.86
Varity_R		0.077
gMVP		0.10

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: chr17-30348256;