dbSNP rs753854746: MUC4:p.Thr3262MetfsTer998 (chr3-195781795-G-GCA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018406.7(MUC4):c.9784_9785insTG(p.Thr3262MetfsTer998) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 0)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC4
NM_018406.7 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

1 publications found

Variant links:

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

MUC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.9784_9785insTG	p.Thr3262MetfsTer998	frameshift_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-3341_83-3340insTG		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-7491_83-7490insTG		intron_variant	Intron 1 of 22		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.9784_9785insTG	p.Thr3262MetfsTer998	frameshift_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.0000115

AC:

AN:

87040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000394

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 MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

137916

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.71e-7

AC:

AN:

1029472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

499546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24698

American (AMR)

AF:

0.00

AC:

AN:

25420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14092

East Asian (EAS)

AF:

0.00

AC:

AN:

10634

South Asian (SAS)

AF:

0.00

AC:

AN:

52294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2696

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841270

Other (OTH)

AF:

0.00

AC:

AN:

38388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000115

AC:

AN:

87116

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

42150

show subpopulations

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

African (AFR)

AF:

0.0000393

AC:

AN:

25436

American (AMR)

AF:

0.00

AC:

AN:

8494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1698

East Asian (EAS)

AF:

0.00

AC:

AN:

2718

South Asian (SAS)

AF:

0.00

AC:

AN:

2808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

38332

Other (OTH)

AF:

0.00

AC:

AN:

1080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), 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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

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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rs753854746

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over