NM_205834.4:c.73G>T

Variant names:

• chr19-35249095-G-T
• rs200943005
• NM_205834.4:c.73G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_205834.4(LSR):​c.73G>T​(p.Val25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,553,334 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V25I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: LSR NM_205834.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200
• Publications: 2 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005397171).
• BP6: Variant 19-35249095-G-T is Benign according to our data. Variant chr19-35249095-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2746821.Status of the report is criteria_provided_single_submitter, 1 stars.

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.73G>T	p.Val25Phe	missense	Exon 1 of 10	NP_991403.2	S4R3V8
	LSR	NM_015925.7		c.73G>T	p.Val25Phe	missense	Exon 1 of 9	NP_057009.4
	LSR	NM_001260489.2		c.73G>T	p.Val25Phe	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.73G>T	p.Val25Phe	missense	Exon 1 of 10	ENSP00000474797.2	S4R3V8
	LSR	ENST00000621372.4	TSL:1	c.217G>T	p.Val73Phe	missense	Exon 1 of 10	ENSP00000480821.1	Q86X29-1
	LSR	ENST00000361790.7	TSL:1	c.73G>T	p.Val25Phe	missense	Exon 1 of 10	ENSP00000354575.3	S4R3V8

Frequencies

GnomAD3 genomes AF: 0.000985 AC: 150 AN: 152224 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000346 AC: 51 AN: 147342 AF XY: 0.000299

Gnomad AFR exome AF: 0.00460

Gnomad AMR exome AF: 0.000341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.000128 AC: 179 AN: 1400990 Hom.: 1 Cov.: 31 AF XY: 0.000121 AC XY: 84 AN XY: 692010

African (AFR) AF: 0.00350 AC: 111 AN: 31736

American (AMR) AF: 0.000344 AC: 12 AN: 34866

Ashkenazi Jewish (ASJ) AF: 0.0000796 AC: 2 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 36366

South Asian (SAS) AF: 0.00 AC: 0 AN: 80102

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48142

Middle Eastern (MID) AF: 0.000231 AC: 1 AN: 4332

European-Non Finnish (NFE) AF: 0.0000305 AC: 33 AN: 1082416

Other (OTH) AF: 0.000328 AC: 19 AN: 57908

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152344 Hom.: 1 Cov.: 33 AF XY: 0.000926 AC XY: 69 AN XY: 74496

African (AFR) AF: 0.00334 AC: 139 AN: 41586

American (AMR) AF: 0.000392 AC: 6 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.00124

ESP6500AA AF: 0.00189 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000236 AC: 24

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.1
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.020
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Benign	0.048	D
Sift4G	Benign	0.12	T
Polyphen		0.052	B
Vest4		0.19
MVP		0.44
MPC		0.26
ClinPred		0.0052	T
GERP RS		2.3
PromoterAI		-0.048	Neutral
Varity_R		0.13
gMVP		0.38
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: rs200943005; hg19: chr19-35739998;