dbSNP rs575666641: MUC3A:p.His2336Gln (chr7-100958787-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005960.2(MUC3A):c.7008C>G(p.His2336Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,454,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict 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. H2336H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 239)

Exomes 𝑓: 0.0000088 ( 0 hom. )

Consequence

MUC3A
NM_005960.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.726

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03782466).

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.7008C>G	p.His2336Gln	missense	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.7008C>G	p.His2336Gln	missense	Exon 2 of 12	ENSP00000368771.5	Q02505-1
MUC3A	ENST00000483366.5	TSL:5	c.7008C>G	p.His2336Gln	missense	Exon 2 of 11	ENSP00000483541.1	Q02505-5
MUC3A	ENST00000868577.1		c.62-1965C>G		intron	N/A	ENSP00000538636.1

Frequencies

GnomAD3 genomes

AF:

0.0000215

AC:

AN:

93012

Hom.:

Cov.:

239

show subpopulations

Gnomad AFR

AF:

0.0000393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000223

AC:

AN:

224526

AF XY:

0.0000322

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000391

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000881

AC:

AN:

1361326

Hom.:

Cov.:

118

AF XY:

0.0000133

AC XY:

AN XY:

676370

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30596

American (AMR)

AF:

0.00

AC:

AN:

40798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23716

East Asian (EAS)

AF:

0.00

AC:

AN:

37508

South Asian (SAS)

AF:

0.00

AC:

AN:

82290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.0000105

AC:

AN:

1050726

Other (OTH)

AF:

0.00

AC:

AN:

55596

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

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:

0.0000215

AC:

AN:

93106

Hom.:

Cov.:

239

AF XY:

0.00

AC XY:

AN XY:

45238

show subpopulations

African (AFR)

AF:

0.0000392

AC:

AN:

25520

American (AMR)

AF:

0.00

AC:

AN:

8542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2124

East Asian (EAS)

AF:

0.00

AC:

AN:

2928

South Asian (SAS)

AF:

0.000437

AC:

AN:

2286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

43630

Other (OTH)

AF:

0.00

AC:

AN:

1232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000527

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.1

(source)

DANN

Benign

0.46

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.23

MetaRNN

Benign

0.038

PhyloP100

-0.73

Sift4G

Benign

0.57

Vest4

0.067

MVP

0.055

GERP RS

-1.2

Varity_R

0.069

gMVP

0.0014

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over