dbSNP rs201090311: LANCL3:p.Asp168Glu (chrX-37572374-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170331.2(LANCL3):c.504C>G(p.Asp168Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,169,692 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 342 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D168D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 27 hem., cov: 23)

Exomes 𝑓: 0.00093 ( 0 hom. 315 hem. )

Consequence

LANCL3
NM_001170331.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.172

Publications

1 publications found

Variant links:

Genes affected

LANCL3 (HGNC:24767): (LanC like family member 3) Predicted to be involved in carbohydrate metabolic process. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LANCL3 links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047790408).

BS2

High Hemizygotes in GnomAd4 at 27 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170331.2. 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
	LANCL3	NM_001170331.2	MANE Select	c.504C>G	p.Asp168Glu	missense	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.504C>G	p.Asp168Glu	missense	Exon 1 of 6	NP_940913.1	Q6ZV70-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LANCL3	ENST00000378619.4	TSL:1 MANE Select	c.504C>G	p.Asp168Glu	missense	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7	TSL:1	c.504C>G	p.Asp168Glu	missense	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146374C>G		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes

AF:

0.000713

AC:

AN:

112164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000278

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00147

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00198

GnomAD2 exomes

AF:

0.000690

AC:

AN:

113008

AF XY:

0.000822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000545

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.000931

AC:

984

AN:

1057473

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

315

AN XY:

344969

show subpopulations

African (AFR)

AF:

0.000198

AC:

AN:

25263

American (AMR)

AF:

0.000451

AC:

AN:

28794

Ashkenazi Jewish (ASJ)

AF:

0.0000535

AC:

AN:

18678

East Asian (EAS)

AF:

0.00

AC:

AN:

27682

South Asian (SAS)

AF:

0.0000399

AC:

AN:

50171

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

36777

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00108

AC:

888

AN:

821470

Other (OTH)

AF:

0.000718

AC:

AN:

44562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000713

AC:

AN:

112219

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

AN XY:

34381

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

30928

American (AMR)

AF:

0.000278

AC:

AN:

10796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3502

South Asian (SAS)

AF:

0.00

AC:

AN:

2676

European-Finnish (FIN)

AF:

0.00147

AC:

AN:

6120

Middle Eastern (MID)

AF:

0.00457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00113

AC:

AN:

53119

Other (OTH)

AF:

0.00196

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000678

Hom.:

Bravo

AF:

0.000612

ExAC

AF:

0.000331

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.1

PhyloP100

-0.17

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.33

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.61

MutPred

0.58

Gain of disorder (P = 0.3932)

MVP

0.38

MPC

1.3

ClinPred

0.17

GERP RS

1.2

Varity_R

0.46

gMVP

0.63

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over