17-32021621-G-C

Position:

• chr17-32021621-G-C

Variant summary

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

The NM_001321350.2(LRRC37B):​c.229G>C​(p.Asp77His) 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. 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: -0.417

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]

LRRC37B (HGNC:):

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=0.14925805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37B	NM_001321350.2	c.229G>C	p.Asp77His	missense_variant	4/15	ENST00000543378.7	NP_001308279.1
LRRC37B	NM_052888.3	c.475G>C	p.Asp159His	missense_variant	1/12		NP_443120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC37B	ENST00000543378.7	c.229G>C	p.Asp77His	missense_variant	4/15	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.475G>C (p.D159H) alteration is located in exon 1 (coding exon 1) of the LRRC37B gene. This alteration results from a G to C substitution at nucleotide position 475, causing the aspartic acid (D) at amino acid position 159 to be replaced by a histidine (H). 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	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.031	.;T;T;.;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.61	T;T;T;T;T;T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;.;.;.;L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.12	.;.;N;N;.;N;N
REVEL	Benign	0.079
Sift	Benign	0.13	.;.;T;T;.;T;T
Sift4G	Pathogenic	0.0	D;D;T;T;T;T;T
Polyphen		0.87	.;.;.;.;.;P;P
Vest4		0.11, 0.065, 0.10, 0.072
MutPred		0.30		.;.;.;.;.;Gain of MoRF binding (P = 0.0544);Gain of MoRF binding (P = 0.0544);
MVP		0.32
MPC		0.33
ClinPred		0.16	T
GERP RS		1.7
Varity_R		0.039
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: chr17-30348640;