chr19-35249090-C-G

Variant names:

• chr19-35249090-C-G
• rs1009148027
• NM_205834.4:c.68C>G

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.68C>G​(p.Ala23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A23E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LSR NM_205834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• 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=0.11227882).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205834.4. 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.68C>G	p.Ala23Gly	missense	Exon 1 of 10	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.68C>G	p.Ala23Gly	missense	Exon 1 of 9	NP_057009.4
	LSR	NM_001260489.2		c.68C>G	p.Ala23Gly	missense	Exon 1 of 9	NP_001247418.2	A0A8Z5DL71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSR	ENST00000605618.6	TSL:1 MANE Select	c.68C>G	p.Ala23Gly	missense	Exon 1 of 10	ENSP00000474797.2	S4R3V8
	LSR	ENST00000621372.4	TSL:1	c.212C>G	p.Ala71Gly	missense	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000361790.7	TSL:1	c.68C>G	p.Ala23Gly	missense	Exon 1 of 10	ENSP00000354575.3	S4R3V8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402506 Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2 AN XY: 692954

African (AFR) AF: 0.00 AC: 0 AN: 31766

American (AMR) AF: 0.00 AC: 0 AN: 35032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 36458

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4386

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083208

Other (OTH) AF: 0.00 AC: 0 AN: 57968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.73
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.41
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.054
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.63	P
Vest4		0.26
MutPred		0.33		Gain of loop (P = 0.0195)
MVP		0.61
MPC		0.41
ClinPred		0.12	T
GERP RS		2.4
PromoterAI		-0.057	Neutral
Varity_R		0.094
gMVP		0.37
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1009148027; hg19: chr19-35739993;