rs370534452

Variant names:

• chr19-35249023-A-C
• rs370534452
• ENST00000621372.4:c.145A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-35249023-A-C
• chr19-35249023-A-G
• chr19-35249023-A-T

Variant summary

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

The ENST00000621372.4(LSR):​c.145A>C​(p.Met49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,572 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LSR ENST00000621372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 10	ENST00000605618.6	NP_991403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSR	ENST00000605618.6	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 10	1	NM_205834.4	ENSP00000474797.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453572 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722558

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 43294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 85662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108644

Other (OTH) AF: 0.00 AC: 0 AN: 59912

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.16	.;T;T;.;.;.;.;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.59	T;T;.;T;T;T;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.;.
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.74	.;.;N;N;N;N;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.010	.;.;D;D;D;T;D;.
Sift4G	Benign	0.46	T;T;T;T;T;T;D;D
Polyphen		0.65	P;P;P;.;.;P;.;.
Vest4		0.59
MutPred		0.39		Loss of catalytic residue at M49 (P = 0.002);Loss of catalytic residue at M49 (P = 0.002);Loss of catalytic residue at M49 (P = 0.002);Loss of catalytic residue at M49 (P = 0.002);Loss of catalytic residue at M49 (P = 0.002);Loss of catalytic residue at M49 (P = 0.002);.;.;
MVP		0.44
MPC		0.38
ClinPred		0.66	D
GERP RS		3.7
PromoterAI		-0.43	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.40
gMVP		0.53
Mutation Taster		=17/183	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs370534452; hg19: chr19-35739926;