ENST00000621372.4:c.130G>T

Variant names:

• chr19-35249008-G-T
• rs367748265
• ENST00000621372.4:c.130G>T

Variant summary

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

The ENST00000621372.4(LSR):​c.130G>T​(p.Ala44Ser) 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 1,456,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A44T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LSR ENST00000621372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• 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=0.07369873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSR	NM_205834.4	MANE Select	c.-15G>T		5_prime_UTR	Exon 1 of 10	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.-15G>T		5_prime_UTR	Exon 1 of 9	NP_057009.4
	LSR	NM_001260489.2		c.-15G>T		5_prime_UTR	Exon 1 of 9	NP_001247418.2	A0A8Z5DL71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSR	ENST00000621372.4	TSL:1	c.130G>T	p.Ala44Ser	missense	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000347609.8	TSL:1	c.130G>T	p.Ala44Ser	missense	Exon 1 of 9	ENSP00000262627.3	Q86X29-2
	LSR	ENST00000605618.6	TSL:1 MANE Select	c.-15G>T		5_prime_UTR	Exon 1 of 10	ENSP00000474797.2	S4R3V8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456750 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724390

African (AFR) AF: 0.00 AC: 0 AN: 33320

American (AMR) AF: 0.00 AC: 0 AN: 43934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 85934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110034

Other (OTH) AF: 0.00 AC: 0 AN: 60086

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.24
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.034
Sift	Benign	0.093	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.030	B
Vest4		0.19
MVP		0.37
MPC		0.20
ClinPred		0.15	T
GERP RS		-0.64
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.068
gMVP		0.20
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs367748265; hg19: chr19-35739911;