dbSNP rs3132580: MUCL3:p.Glu1295Lys (chr6-30952347-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080870.4(MUCL3):c.3883G>A(p.Glu1295Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,614,074 control chromosomes in the GnomAD database, including 15,343 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 801 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14542 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.989

Publications

54 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015239418).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4 link	c.3883G>A	p.Glu1295Lys	missense_variant	Exon 2 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1 link	n.256+15C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MUCL3	ENST00000462446.6 link	c.3883G>A	p.Glu1295Lys	missense_variant	Exon 2 of 3	5	NM_080870.4	ENSP00000417182.1	E9PEI6
HCG21	ENST00000419481.1 link	n.224+720C>T		intron_variant	Intron 2 of 2	3
SFTA2	ENST00000634371.2 link	n.513+15C>T		intron_variant	Intron 4 of 5	5			A0A0U1RRK6

Frequencies

GnomAD3 genomes

AF:

0.0909

AC:

13819

AN:

152096

Hom.:

801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.0368

Gnomad ASJ

AF:

0.0654

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0764

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.0703

GnomAD2 exomes

AF:

0.0804

AC:

20202

AN:

251246

AF XY:

0.0795

show subpopulations

Gnomad AFR exome

AF:

0.0636

Gnomad AMR exome

AF:

0.0314

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.0755

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.129

AC:

189048

AN:

1461860

Hom.:

14542

Cov.:

AF XY:

0.126

AC XY:

91444

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0617

AC:

2067

AN:

33474

American (AMR)

AF:

0.0326

AC:

1458

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

1749

AN:

26136

East Asian (EAS)

AF:

0.0126

AC:

501

AN:

39700

South Asian (SAS)

AF:

0.0157

AC:

1356

AN:

86252

European-Finnish (FIN)

AF:

0.0792

AC:

4231

AN:

53418

Middle Eastern (MID)

AF:

0.0376

AC:

217

AN:

5768

European-Non Finnish (NFE)

AF:

0.153

AC:

170512

AN:

1111998

Other (OTH)

AF:

0.115

AC:

6957

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10932

21864

32797

43729

54661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6082

12164

18246

24328

30410

<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:

0.0909

AC:

13829

AN:

152214

Hom.:

801

Cov.:

AF XY:

0.0841

AC XY:

6256

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0621

AC:

2579

AN:

41536

American (AMR)

AF:

0.0366

AC:

560

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0654

AC:

227

AN:

3470

East Asian (EAS)

AF:

0.0201

AC:

104

AN:

5184

South Asian (SAS)

AF:

0.0129

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0764

AC:

810

AN:

10596

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9201

AN:

67992

Other (OTH)

AF:

0.0691

AC:

146

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

652

1305

1957

2610

3262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.123

Hom.:

4154

Bravo

AF:

0.0889

TwinsUK

AF:

0.169

AC:

625

ALSPAC

AF:

0.162

AC:

623

ESP6500AA

AF:

0.0699

AC:

308

ESP6500EA

AF:

0.132

AC:

1135

ExAC

AF:

0.0801

AC:

9720

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.018

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0030

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.40

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.97

PhyloP100

-0.99

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.23

.;N;.

REVEL

Benign

0.0050

Sift4G

Benign

0.31

.;T;T

Polyphen

0.032

.;B;.

Vest4

0.067, 0.010

MPC

0.61

ClinPred

0.000037

GERP RS

-7.2

Varity_R

0.019

gMVP

0.11

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over