Genetic Variant NM_005960.2:c.6981G>A (chr7-100958760-G-A) – 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.6981G>A(p.Ser2327Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000861 in 800,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.18 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00070 ( 0 hom. )

Consequence

MUC3A
NM_005960.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

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 7-100958760-G-A is Benign according to our data. Variant chr7-100958760-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657783.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

128

AN:

712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.261

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.200

GnomAD2 exomes

AF:

0.0000850

AC:

AN:

164754

AF XY:

0.000117

show subpopulations

Gnomad AFR exome

AF:

0.000121

Gnomad AMR exome

AF:

0.0000888

Gnomad ASJ exome

AF:

0.000259

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000702

AC:

561

AN:

799350

Hom.:

Cov.:

102

AF XY:

0.000721

AC XY:

277

AN XY:

384338

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

16084

American (AMR)

AF:

0.000382

AC:

AN:

10484

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

118

AN:

11016

East Asian (EAS)

AF:

0.00

AC:

AN:

20134

South Asian (SAS)

AF:

0.000253

AC:

AN:

27630

European-Finnish (FIN)

AF:

0.00367

AC:

AN:

14696

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2828

European-Non Finnish (NFE)

AF:

0.000525

AC:

349

AN:

664560

Other (OTH)

AF:

0.000815

AC:

AN:

31918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

114

142

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:

0.179

AC:

128

AN:

714

Hom.:

Cov.:

AF XY:

0.203

AC XY:

AN XY:

374

show subpopulations

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

African (AFR)

AF:

0.0530

AC:

AN:

132

American (AMR)

AF:

0.0333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.118

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.261

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.224

AC:

AN:

366

Other (OTH)

AF:

0.200

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: 0.396

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:

0.500

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

8.9

(source)

DANN

Benign

0.64

PhyloP100

-5.1

Mutation Taster

=100/0

polymorphism

(source)

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