dbSNP rs2240804: MUCL3:p.Arg1393Gln (chr6-30953113-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.4178G>A(p.Arg1393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,778 control chromosomes in the GnomAD database, including 87,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.26 ( 6222 hom., cov: 33)

Exomes 𝑓: 0.33 ( 81344 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.183

Publications

42 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=0.0034334064).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4 link	c.4178G>A	p.Arg1393Gln	missense_variant	Exon 3 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1 link	n.87-582C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MUCL3	ENST00000462446.6 link	c.4178G>A	p.Arg1393Gln	missense_variant	Exon 3 of 3	5	NM_080870.4	ENSP00000417182.1	E9PEI6
HCG21	ENST00000419481.1 link	n.178C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
SFTA2	ENST00000634371.2 link	n.288C>T		non_coding_transcript_exon_variant	Exon 3 of 6	5			A0A0U1RRK6

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39266

AN:

152100

Hom.:

6227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0815

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.255

GnomAD2 exomes

AF:

0.294

AC:

73813

AN:

250770

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.362

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.327

AC:

477577

AN:

1461562

Hom.:

81344

Cov.:

AF XY:

0.326

AC XY:

236796

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.0713

AC:

2388

AN:

33474

American (AMR)

AF:

0.206

AC:

9204

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9515

AN:

26132

East Asian (EAS)

AF:

0.188

AC:

7457

AN:

39698

South Asian (SAS)

AF:

0.229

AC:

19732

AN:

86226

European-Finnish (FIN)

AF:

0.384

AC:

20452

AN:

53268

Middle Eastern (MID)

AF:

0.309

AC:

1774

AN:

5732

European-Non Finnish (NFE)

AF:

0.350

AC:

389206

AN:

1111944

Other (OTH)

AF:

0.296

AC:

17849

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19829

39658

59488

79317

99146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12114

24228

36342

48456

60570

<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:

0.258

AC:

39266

AN:

152216

Hom.:

6222

Cov.:

AF XY:

0.258

AC XY:

19176

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0816

AC:

3390

AN:

41562

American (AMR)

AF:

0.226

AC:

3462

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1372

AN:

3472

East Asian (EAS)

AF:

0.180

AC:

932

AN:

5174

South Asian (SAS)

AF:

0.213

AC:

1027

AN:

4830

European-Finnish (FIN)

AF:

0.391

AC:

4137

AN:

10592

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24042

AN:

67968

Other (OTH)

AF:

0.252

AC:

533

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1451

2902

4352

5803

7254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.320

Hom.:

27571

Bravo

AF:

0.239

TwinsUK

AF:

0.348

AC:

1290

ALSPAC

AF:

0.357

AC:

1375

ESP6500AA

AF:

0.0976

AC:

430

ESP6500EA

AF:

0.362

AC:

3114

ExAC

AF:

0.297

AC:

36121

Asia WGS

AF:

0.152

AC:

534

AN:

3478

EpiCase

AF:

0.359

EpiControl

AF:

0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.18

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.67

.;N;.

REVEL

Benign

0.058

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

0.35

.;B;.

Vest4

0.056, 0.021

MPC

0.57

ClinPred

0.027

GERP RS

-1.6

Varity_R

0.044

gMVP

0.18

Mutation Taster

=98/2

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