dbSNP rs532413302: MUC21:p.Ala117Ala (chr6-30986526-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001010909.5(MUC21):c.351C>T(p.Ala117Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,586,744 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000099 ( 3 hom. )

Consequence

MUC21
NM_001010909.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.46

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-30986526-C-T is Benign according to our data. Variant chr6-30986526-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3898073.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.46 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010909.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC21	NM_001010909.5	MANE Select	c.351C>T	p.Ala117Ala	synonymous	Exon 2 of 3	NP_001010909.2	Q5SSG8-1
	MUC21	NR_130720.3		n.734C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC21	ENST00000376296.3	TSL:1 MANE Select	c.351C>T	p.Ala117Ala	synonymous	Exon 2 of 3	ENSP00000365473.3	Q5SSG8-1
	MUC21	ENST00000486149.2	TSL:1	c.-1012C>T		5_prime_UTR	Exon 2 of 3	ENSP00000457640.1	A0A0C4DGM6

Frequencies

GnomAD3 genomes

AF:

0.000816

AC:

123

AN:

150774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000965

GnomAD2 exomes

AF:

0.000251

AC:

AN:

251282

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.00352

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000989

AC:

142

AN:

1435856

Hom.:

Cov.:

168

AF XY:

0.0000644

AC XY:

AN XY:

713960

show subpopulations

African (AFR)

AF:

0.00388

AC:

124

AN:

31986

American (AMR)

AF:

0.0000932

AC:

AN:

42904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24836

East Asian (EAS)

AF:

0.00

AC:

AN:

37242

South Asian (SAS)

AF:

0.00

AC:

AN:

84558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1097528

Other (OTH)

AF:

0.000187

AC:

AN:

58760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000822

AC:

124

AN:

150888

Hom.:

Cov.:

AF XY:

0.000813

AC XY:

AN XY:

73758

show subpopulations

African (AFR)

AF:

0.00282

AC:

115

AN:

40828

American (AMR)

AF:

0.000330

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67736

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000560

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.44

PhyloP100

-2.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over