Genetic Variant MUC3A:p.Pro2407Pro (chr7-100959000-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005960.2(MUC3A):c.7221T>C(p.Pro2407Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC3A
NM_005960.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.94

Publications

0 publications found

Variant links:

Genes affected

MUC3A (HGNC:7513): (mucin 3A, cell surface associated) The mucin genes encode epithelial glycoproteins, some of which are secreted and some membrane bound. Each of the genes contains at least one large domain of tandemly repeated sequence that encodes the peptide sequence rich in serine and/or threonine residues, which carries most of the O-linked glycosylation (Gendler and Spicer, 1995 [PubMed 7778880]).[supplied by OMIM, Aug 2008]

MUC3A links:

LOC105375431 (HGNC:):

LOC105375431 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 7-100959000-T-C is Benign according to our data. Variant chr7-100959000-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2657788.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005960.2. 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
	MUC3A	NM_005960.2	MANE Select	c.7221T>C	p.Pro2407Pro	synonymous	Exon 2 of 12	NP_005951.1	Q02505-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC3A	ENST00000379458.9	TSL:5 MANE Select	c.7221T>C	p.Pro2407Pro	synonymous	Exon 2 of 12	ENSP00000368771.5	Q02505-1
MUC3A	ENST00000483366.5	TSL:5	c.7221T>C	p.Pro2407Pro	synonymous	Exon 2 of 11	ENSP00000483541.1	Q02505-5
MUC3A	ENST00000868577.1		c.62-1752T>C		intron	N/A	ENSP00000538636.1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

AN:

1242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00926

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

214126

AF XY:

0.0000337

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000313

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000386

AC:

AN:

1294554

Hom.:

Cov.:

100

AF XY:

0.00000315

AC XY:

AN XY:

634146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29346

American (AMR)

AF:

0.00

AC:

AN:

36254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22274

East Asian (EAS)

AF:

0.00

AC:

AN:

34350

South Asian (SAS)

AF:

0.00

AC:

AN:

63156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4958

European-Non Finnish (NFE)

AF:

0.00000490

AC:

AN:

1020198

Other (OTH)

AF:

0.00

AC:

AN:

52864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0105

AC:

AN:

1244

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

AN XY:

594

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0127

AC:

AN:

316

American (AMR)

AF:

0.0145

AC:

AN:

138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0556

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00926

AC:

AN:

540

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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:

0.271

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

-1.0

CADD

Benign

4.2

(source)

DANN

Benign

0.30

PhyloP100

-2.9

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over