NM_205834.4:c.34C>A

Variant names:

• chr19-35249056-C-A
• rs373009795
• NM_205834.4:c.34C>A

Variant summary

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

The NM_205834.4(LSR):​c.34C>A​(p.Leu12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L12L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LSR NM_205834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• 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=0.090216905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4	c.34C>A	p.Leu12Met	missense_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.34C>A	p.Leu12Met	missense_variant	Exon 1 of 10	1	NM_205834.4	ENSP00000474797.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1428328 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708024

African (AFR) AF: 0.00 AC: 0 AN: 32700

American (AMR) AF: 0.00 AC: 0 AN: 38770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25564

East Asian (EAS) AF: 0.00 AC: 0 AN: 38108

South Asian (SAS) AF: 0.00 AC: 0 AN: 83352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4826

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1096432

Other (OTH) AF: 0.00 AC: 0 AN: 58996

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.2
DANN	Benign	0.90
DEOGEN2	Benign	0.12	.;T;T;.;.;.;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.51	T;T;.;T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.090	T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.90	L;L;L;L;L;.;.
PhyloP100		-0.47
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.31	.;.;N;N;N;N;.
REVEL	Benign	0.048
Sift	Benign	0.17	.;.;T;T;T;T;.
Sift4G	Benign	0.26	T;T;T;T;T;T;T
Polyphen		0.37	B;B;B;.;.;.;.
Vest4		0.12
MutPred		0.20		Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);Gain of MoRF binding (P = 0.0838);.;.;
MVP		0.31
MPC		0.18
ClinPred		0.13	T
GERP RS		2.3
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.061
gMVP		0.26
Mutation Taster		=98/2	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

dbSNP: rs373009795; hg19: chr19-35739959;