NM_005570.4:c.116T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005570.4(LMAN1):c.116T>C(p.Val39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,613,990 control chromosomes in the GnomAD database, including 6,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 797 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5357 hom. )

Consequence

LMAN1
NM_005570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.253

Publications

21 publications found

Variant links:

Genes affected

LMAN1 (HGNC:6631): (lectin, mannose binding 1) The protein encoded by this gene is a membrane mannose-specific lectin that cycles between the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment, and cis-Golgi, functioning as a cargo receptor for glycoprotein transport. The protein has an N-terminal signal sequence, a calcium-dependent and pH-sensitive carbohydrate recognition domain, a stalk region that functions in oligomerization, a transmembrane domain, and a short cytoplasmic domain required for organelle targeting. Allelic variants of this gene are associated with the autosomal recessive disorder combined factor V-factor VIII deficiency. [provided by RefSeq, Jul 2015]

LMAN1 Gene-Disease associations (from GenCC):

factor V and factor VIII, combined deficiency of, type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
combined deficiency of factor V and factor VIII
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LMAN1 links:

ENSG00000267677 (HGNC:):

ENSG00000267677 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016942322).

BP6

Variant 18-59359129-A-G is Benign according to our data. Variant chr18-59359129-A-G is described in ClinVar as Benign. ClinVar VariationId is 259791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005570.4. 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
	LMAN1	NM_005570.4	MANE Select	c.116T>C	p.Val39Ala	missense	Exon 1 of 13	NP_005561.1	P49257

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMAN1	ENST00000251047.6	TSL:1 MANE Select	c.116T>C	p.Val39Ala	missense	Exon 1 of 13	ENSP00000251047.4	P49257
LMAN1	ENST00000963587.1		c.116T>C	p.Val39Ala	missense	Exon 1 of 13	ENSP00000633646.1
LMAN1	ENST00000904707.1		c.116T>C	p.Val39Ala	missense	Exon 1 of 13	ENSP00000574766.1

Frequencies

GnomAD3 genomes

AF:

0.0932

AC:

14178

AN:

152134

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0404

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.0685

AC:

17210

AN:

251136

AF XY:

0.0678

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0863

Gnomad OTH exome

AF:

0.0776

GnomAD4 exome

AF:

0.0825

AC:

120535

AN:

1461738

Hom.:

5357

Cov.:

AF XY:

0.0814

AC XY:

59200

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.146

AC:

4898

AN:

33476

American (AMR)

AF:

0.0512

AC:

2288

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2815

AN:

26124

East Asian (EAS)

AF:

0.000151

AC:

AN:

39694

South Asian (SAS)

AF:

0.0427

AC:

3686

AN:

86256

European-Finnish (FIN)

AF:

0.0365

AC:

1947

AN:

53380

Middle Eastern (MID)

AF:

0.139

AC:

803

AN:

5768

European-Non Finnish (NFE)

AF:

0.0890

AC:

98998

AN:

1111932

Other (OTH)

AF:

0.0844

AC:

5094

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7225

14451

21676

28902

36127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3668

7336

11004

14672

18340

<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:

0.0932

AC:

14186

AN:

152252

Hom.:

797

Cov.:

AF XY:

0.0891

AC XY:

6633

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.138

AC:

5752

AN:

41556

American (AMR)

AF:

0.0774

AC:

1184

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

347

AN:

3466

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0396

AC:

191

AN:

4826

European-Finnish (FIN)

AF:

0.0311

AC:

330

AN:

10608

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0896

AC:

6090

AN:

68000

Other (OTH)

AF:

0.101

AC:

213

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

671

1342

2014

2685

3356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0946

Hom.:

1102

Bravo

AF:

0.0984

TwinsUK

AF:

0.0863

AC:

320

ALSPAC

AF:

0.0929

AC:

358

ESP6500AA

AF:

0.129

AC:

567

ESP6500EA

AF:

0.0865

AC:

744

ExAC

AF:

0.0698

AC:

8474

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0960

EpiControl

AF:

0.0959

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Factor V and factor VIII, combined deficiency of, type 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.072

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.25

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.81

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.021

MPC

0.24

ClinPred

0.0020

GERP RS

-5.1

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(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