Genetic Variant MUCL3:p.Leu1154Leu (chr6-30951924-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_080870.4(MUCL3):c.3460T>C(p.Leu1154Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,612,734 control chromosomes in the GnomAD database, including 96,345 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6987 hom., cov: 31)

Exomes 𝑓: 0.35 ( 89358 hom. )

Consequence

MUCL3
NM_080870.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.71

Publications

27 publications found

Variant links:

Genes affected

MUCL3 (HGNC:21666): (mucin like 3) Predicted to be located in cytoplasm and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUCL3 links:

HCG21 (HGNC:31335): (HLA complex group 21)

HCG21 links:

SFTA2 (HGNC:18386): (surfactant associated 2) Predicted to be located in Golgi apparatus; extracellular region; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

SFTA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-5.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4 link	c.3460T>C	p.Leu1154Leu	synonymous_variant	Exon 2 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1 link	n.256+438A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MUCL3	ENST00000462446.6 link	c.3460T>C	p.Leu1154Leu	synonymous_variant	Exon 2 of 3	5	NM_080870.4	ENSP00000417182.1
HCG21	ENST00000419481.1 link	n.224+1143A>G		intron_variant	Intron 2 of 2	3
SFTA2	ENST00000634371.2 link	n.513+438A>G		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43172

AN:

151238

Hom.:

6988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.285

GnomAD2 exomes

AF:

0.324

AC:

81094

AN:

250296

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.374

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.345

AC:

504354

AN:

1461378

Hom.:

89358

Cov.:

AF XY:

0.346

AC XY:

251193

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.119

AC:

3967

AN:

33402

American (AMR)

AF:

0.221

AC:

9873

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9763

AN:

26128

East Asian (EAS)

AF:

0.258

AC:

10227

AN:

39694

South Asian (SAS)

AF:

0.302

AC:

26065

AN:

86204

European-Finnish (FIN)

AF:

0.388

AC:

20703

AN:

53362

Middle Eastern (MID)

AF:

0.332

AC:

1913

AN:

5768

European-Non Finnish (NFE)

AF:

0.362

AC:

402528

AN:

1111864

Other (OTH)

AF:

0.320

AC:

19315

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

22466

44931

67397

89862

112328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12574

25148

37722

50296

62870

<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:

0.285

AC:

43191

AN:

151356

Hom.:

6987

Cov.:

AF XY:

0.286

AC XY:

21184

AN XY:

73960

show subpopulations

African (AFR)

AF:

0.128

AC:

5275

AN:

41188

American (AMR)

AF:

0.246

AC:

3742

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1394

AN:

3464

East Asian (EAS)

AF:

0.275

AC:

1416

AN:

5148

South Asian (SAS)

AF:

0.297

AC:

1419

AN:

4778

European-Finnish (FIN)

AF:

0.396

AC:

4139

AN:

10456

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24818

AN:

67794

Other (OTH)

AF:

0.284

AC:

596

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1459

2918

4378

5837

7296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.341

Hom.:

35006

Bravo

AF:

0.267

Asia WGS

AF:

0.251

AC:

877

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.66

(source)

DANN

Benign

0.82

PhyloP100

-5.7

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over