dbSNP rs12179536: MUC22:p.Ile128Val (chr6-31025813-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001395414.1(MUC22):c.382A>G(p.Ile128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,534,794 control chromosomes in the GnomAD database, including 27,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I128M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.16 ( 2397 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25494 hom. )

Consequence

MUC22
NM_001395414.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320

Publications

24 publications found

Variant links:

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUC22 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=1.0362754E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC22	NM_001395414.1 link	c.382A>G	p.Ile128Val	missense_variant	Exon 2 of 4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1 link	c.391A>G	p.Ile131Val	missense_variant	Exon 3 of 5		NP_001305413.1	E2RYF6
MUC22	NM_001198815.1 link	c.382A>G	p.Ile128Val	missense_variant	Exon 3 of 5		NP_001185744.1	E2RYF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1 link	c.382A>G	p.Ile128Val	missense_variant	Exon 2 of 4	2	NM_001395414.1	ENSP00000455906.1		E2RYF6

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25052

AN:

151954

Hom.:

2393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.223

AC:

28617

AN:

128570

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.0816

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.182

AC:

252111

AN:

1382720

Hom.:

25494

Cov.:

AF XY:

0.188

AC XY:

128369

AN XY:

682262

show subpopulations

African (AFR)

AF:

0.0819

AC:

2586

AN:

31576

American (AMR)

AF:

0.276

AC:

9846

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3631

AN:

25178

East Asian (EAS)

AF:

0.316

AC:

11298

AN:

35724

South Asian (SAS)

AF:

0.323

AC:

25591

AN:

79192

European-Finnish (FIN)

AF:

0.161

AC:

5414

AN:

33656

Middle Eastern (MID)

AF:

0.205

AC:

1165

AN:

5694

European-Non Finnish (NFE)

AF:

0.170

AC:

183056

AN:

1078132

Other (OTH)

AF:

0.165

AC:

9524

AN:

57880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13689

27378

41068

54757

68446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.165

AC:

25061

AN:

152074

Hom.:

2397

Cov.:

AF XY:

0.168

AC XY:

12503

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0891

AC:

3696

AN:

41490

American (AMR)

AF:

0.244

AC:

3720

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3470

East Asian (EAS)

AF:

0.247

AC:

1278

AN:

5168

South Asian (SAS)

AF:

0.300

AC:

1439

AN:

4798

European-Finnish (FIN)

AF:

0.160

AC:

1698

AN:

10592

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12248

AN:

67968

Other (OTH)

AF:

0.166

AC:

349

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1049

2098

3148

4197

5246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.182

Hom.:

10908

Bravo

AF:

0.165

TwinsUK

AF:

0.172

AC:

636

ALSPAC

AF:

0.161

AC:

620

ExAC

AF:

0.200

AC:

3588

Asia WGS

AF:

0.258

AC:

893

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.3

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.0056

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

MetaRNN

Benign

0.00010

MutationAssessor

Benign

0.0

PhyloP100

0.32

PrimateAI

Benign

0.15

PROVEAN

Benign

-0.12

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

Vest4

0.010

GERP RS

-3.0

Varity_R

0.090

gMVP

0.0031

Mutation Taster

=97/3

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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rs12179536

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