17-32021348-G-T

Variant names:

• chr17-32021348-G-T
• ENST00000341671.12:c.202G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052888.3(LRRC37B):​c.202G>T​(p.Ala68Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC37B NM_052888.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054656774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37B	NM_001321350.2	c.1-45G>T		intron_variant	Intron 3 of 14	ENST00000543378.7	NP_001308279.1
LRRC37B	NM_052888.3	c.202G>T	p.Ala68Ser	missense_variant	Exon 1 of 12		NP_443120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC37B	ENST00000543378.7	c.1-45G>T		intron_variant	Intron 3 of 14	2	NM_001321350.2	ENSP00000443345.2

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

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.202G>T (p.A68S) 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 202, causing the alanine (A) at amino acid position 68 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	0.082
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.94
DEOGEN2	Benign	0.0077	.;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.42	T;T;T;.
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;.;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.13	N;.;N;N
REVEL	Benign	0.012
Sift	Benign	0.099	T;.;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.055	.;.;B;B
Vest4		0.054
MutPred		0.15		.;.;Gain of glycosylation at A68 (P = 0.003);Gain of glycosylation at A68 (P = 0.003);
MVP		0.093
MPC		0.050
ClinPred		0.058	T
GERP RS		0.78
Varity_R		0.034
gMVP		0.035

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-30348367;