dbSNP rs886403: MUC21:c.*1647T>C (chr6-30989841-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001010909.5(MUC21):c.*1647T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,178 control chromosomes in the GnomAD database, including 4,271 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 0.22 ( 4271 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

MUC21
NM_001010909.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

29 publications found

Variant links:

Genes affected

MUC21 (HGNC:21661): (mucin 21, cell surface associated) This gene encodes a large membrane-bound glycoprotein which is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. The encoded protein contains an N-terminal signal sequence, an extracellular mucin domain, a stem domain, a transmembrane domain, and a C-terminal cytoplasmic tail domain. The mucin domain contains O-glycosylation sites and is polymorphic with isoforms containing a variable number of nonidentical proline-, threonine-, and serine-rich tandem repeats of 15 amino acids each. The aberrent expression of this gene is associated with lung adenocarcinoma. [provided by RefSeq, May 2017]

MUC21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC21	NM_001010909.5 link	c.*1647T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000376296.3	NP_001010909.2
MUC21	NR_130720.3 link	n.3731T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC21	ENST00000376296.3 link	c.*1647T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001010909.5	ENSP00000365473.3

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34021

AN:

152052

Hom.:

4272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.0562

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.224

AC:

34027

AN:

152170

Hom.:

4271

Cov.:

AF XY:

0.216

AC XY:

16080

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.145

AC:

6002

AN:

41532

American (AMR)

AF:

0.237

AC:

3623

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1022

AN:

3470

East Asian (EAS)

AF:

0.0563

AC:

292

AN:

5182

South Asian (SAS)

AF:

0.111

AC:

534

AN:

4826

European-Finnish (FIN)

AF:

0.232

AC:

2458

AN:

10592

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19264

AN:

67970

Other (OTH)

AF:

0.241

AC:

509

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1346

2692

4037

5383

6729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.265

Hom.:

13863

Bravo

AF:

0.228

Asia WGS

AF:

0.0890

AC:

310

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.8

(source)

DANN

Benign

0.48

PhyloP100

0.31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over