ENST00000361790.7:c.-35G>T

Variant names:

• chr19-35248988-G-T
• ENST00000361790.7:c.-35G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000361790.7(LSR):​c.-35G>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSR ENST00000361790.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.750
• Publications: 0 publications found

Genes affected

LSR (HGNC:29572): (lipolysis stimulated lipoprotein receptor) Predicted to be involved in several processes, including establishment of skin barrier; protein localization to tricellular tight junction; and tricellular tight junction assembly. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124071866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4	c.-35G>T		upstream_gene_variant		ENST00000605618.6	NP_991403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSR	ENST00000605618.6	c.-35G>T		upstream_gene_variant		1	NM_205834.4	ENSP00000474797.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110G>T (p.R37M) alteration is located in exon 1 (coding exon 1) of the LSR gene. This alteration results from a G to T substitution at nucleotide position 110, causing the arginine (R) at amino acid position 37 to be replaced by a methionine (M). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.093	.;T;T;.;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.51	T;T;.;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N
PhyloP100		0.75
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.19	.;.;N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.061	.;.;T;D;D;T
Sift4G	Benign	0.083	T;T;T;T;T;T
Polyphen		0.55	P;B;B;.;.;B
Vest4		0.27
MutPred		0.32		Loss of methylation at R37 (P = 0.0121);Loss of methylation at R37 (P = 0.0121);Loss of methylation at R37 (P = 0.0121);Loss of methylation at R37 (P = 0.0121);Loss of methylation at R37 (P = 0.0121);Loss of methylation at R37 (P = 0.0121);
MVP		0.57
MPC		0.27
ClinPred		0.097	T
GERP RS		1.4
PromoterAI		0.050	Neutral
Varity_R		0.063
gMVP		0.39
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr19-35739891;