rs35564267

Variant names:

• chr19-35249038-G-A
• rs35564267
• NM_205834.4:c.16G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35249038-G-A
• chr19-35249038-G-C
• chr19-35249038-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_205834.4(LSR):​c.16G>A​(p.Gly6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,442,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G6E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: LSR NM_205834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042260617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSR	NM_205834.4	c.16G>A	p.Gly6Ser	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.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 10	1	NM_205834.4	ENSP00000474797.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000555 AC: 8 AN: 1442572 Hom.: 0 Cov.: 31 AF XY: 0.00000698 AC XY: 5 AN XY: 716126

African (AFR) AF: 0.00 AC: 0 AN: 33030

American (AMR) AF: 0.00 AC: 0 AN: 41398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25790

East Asian (EAS) AF: 0.0000514 AC: 2 AN: 38898

South Asian (SAS) AF: 0.00 AC: 0 AN: 84696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5110

European-Non Finnish (NFE) AF: 0.00000544 AC: 6 AN: 1103362

Other (OTH) AF: 0.00 AC: 0 AN: 59512

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.18
DANN	Benign	0.93
DEOGEN2	Benign	0.12	.;T;T;.;.;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.69	T;T;.;T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.042	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;N;N;N;N;.;.
PhyloP100		-1.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.38	.;.;N;N;N;N;.
REVEL	Benign	0.029
Sift	Benign	0.44	.;.;T;T;T;T;.
Sift4G	Benign	0.88	T;T;T;T;T;T;T
Polyphen		0.013	B;B;B;.;.;.;.
Vest4		0.067
MutPred		0.31		Gain of glycosylation at G54 (P = 0.0053);Gain of glycosylation at G54 (P = 0.0053);Gain of glycosylation at G54 (P = 0.0053);Gain of glycosylation at G54 (P = 0.0053);Gain of glycosylation at G54 (P = 0.0053);.;.;
MVP		0.36
MPC		0.20
ClinPred		0.060	T
GERP RS		-2.9
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.039
gMVP		0.39
Mutation Taster		=99/1	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: rs35564267; hg19: chr19-35739941;