Genetic Variant MUC3A:p.Ser2327Ser (chr7-100958760-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_005960.2(MUC3A):c.6981G>T(p.Ser2327Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 800,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S2327S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

MUC3A
NM_005960.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.09

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP7

Synonymous conserved (PhyloP=-5.09 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.6981G>T	p.Ser2327Ser	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.6981G>T	p.Ser2327Ser	synonymous	Exon 2 of 12	ENSP00000368771.5	Q02505-1
MUC3A	ENST00000483366.5	TSL:5	c.6981G>T	p.Ser2327Ser	synonymous	Exon 2 of 11	ENSP00000483541.1	Q02505-5
MUC3A	ENST00000868577.1		c.62-1992G>T		intron	N/A	ENSP00000538636.1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

AN:

794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

164754

AF XY:

0.0000106

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000250

AC:

AN:

799480

Hom.:

Cov.:

102

AF XY:

0.00000260

AC XY:

AN XY:

384412

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

16084

American (AMR)

AF:

0.00

AC:

AN:

10492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11020

East Asian (EAS)

AF:

0.00

AC:

AN:

20142

South Asian (SAS)

AF:

0.00

AC:

AN:

27642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

664642

Other (OTH)

AF:

0.00

AC:

AN:

31922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.00126

AC:

AN:

794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

404

show subpopulations

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

African (AFR)

AF:

0.00676

AC:

AN:

148

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

100

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

404

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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.2

(source)

DANN

Benign

0.46

PhyloP100

-5.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over