chr17-32021729-G-T

Position:

• chr17-32021729-G-T

Variant summary

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

The NM_001321350.2(LRRC37B):​c.337G>T​(p.Asp113Tyr) 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: 0.237

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=0.1827679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37B	NM_001321350.2	c.337G>T	p.Asp113Tyr	missense_variant	4/15	ENST00000543378.7
LRRC37B	NM_052888.3	c.583G>T	p.Asp195Tyr	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37B	ENST00000543378.7	c.337G>T	p.Asp113Tyr	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

Jul 20, 2022

The c.583G>T (p.D195Y) 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 583, causing the aspartic acid (D) at amino acid position 195 to be replaced by a tyrosine (Y). 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	0.23
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.18	.;T;T;.;T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.78	T;T;T;T;T;T;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	.;.;.;.;.;M;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.0	.;.;D;D;.;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	.;.;D;D;.;D;D
Sift4G	Uncertain	0.011	D;D;T;T;T;T;T
Polyphen		0.79	.;.;.;.;.;P;P
Vest4		0.18, 0.18, 0.22, 0.14, 0.16
MutPred		0.29		.;.;.;.;.;Loss of disorder (P = 0.0168);Loss of disorder (P = 0.0168);
MVP		0.13
MPC		0.065
ClinPred		0.39	T
GERP RS		1.9
Varity_R		0.14
gMVP		0.41

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: rs768726319; hg19: chr17-30348748; COSMIC: COSV58951647; COSMIC: COSV58951647;