chr19-35248967-G-C

Variant names:

• chr19-35248967-G-C
• ENST00000621372.4:c.89G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000621372.4(LSR):​c.89G>C​(p.Arg30Pro) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSR ENST00000621372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3267278).

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.-56G>C		upstream_gene	N/A	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.-56G>C		upstream_gene	N/A	NP_057009.4
	LSR	NM_001260489.2		c.-56G>C		upstream_gene	N/A	NP_001247418.2	A0A8Z5DL71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSR	ENST00000621372.4	TSL:1	c.89G>C	p.Arg30Pro	missense	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000347609.8	TSL:1	c.89G>C	p.Arg30Pro	missense	Exon 1 of 9	ENSP00000262627.3	Q86X29-2
	LSR	ENST00000361790.7	TSL:1	c.-56G>C		5_prime_UTR	Exon 1 of 10	ENSP00000354575.3	S4R3V8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0045	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.43		Loss of MoRF binding (P = 6e-04)
MVP		0.71
MPC		0.91
ClinPred		0.92	D
GERP RS		2.6
PromoterAI		0.066	Neutral
Varity_R		0.36
gMVP		0.29
Mutation Taster		=76/24	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: chr19-35739870;