Genetic Variant MUC7:p.Asn80Lys (chr4-70480984-C-A) – 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_152291.3(MUC7):c.240C>A(p.Asn80Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MUC7
NM_152291.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.88

Publications

27 publications found

Variant links:

Genes affected

MUC7 (HGNC:7518): (mucin 7, secreted) This gene encodes a small salivary mucin, which is thought to play a role in facilitating the clearance of bacteria in the oral cavity and to aid in mastication, speech, and swallowing. The central domain of this glycoprotein contains tandem repeats, each composed of 23 amino acids. This antimicrobial protein has antibacterial and antifungal activity. The most common allele contains 6 repeats, and some alleles may be associated with susceptibility to asthma. Alternatively spliced transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Oct 2014]

MUC7 links:

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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=0.060606062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MUC7	NM_152291.3 link	c.240C>A	p.Asn80Lys	missense_variant	Exon 3 of 3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2 link	c.240C>A	p.Asn80Lys	missense_variant	Exon 4 of 4		NP_001138478.1
MUC7	NM_001145007.2 link	c.240C>A	p.Asn80Lys	missense_variant	Exon 4 of 4		NP_001138479.1
MUC7	XM_047415723.1 link	c.240C>A	p.Asn80Lys	missense_variant	Exon 4 of 4		XP_047271679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC7	ENST00000304887.6 link	c.240C>A	p.Asn80Lys	missense_variant	Exon 3 of 3	1	NM_152291.3	ENSP00000302021.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111926

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.021

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.010

T;.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.32

T;T;.;.

M_CAP

Benign

0.0033

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;N;N

PhyloP100

-2.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.51

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0060

B;.;B;B

Vest4

0.016

MutPred

0.13

Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);

MVP

0.19

MPC

0.060

ClinPred

0.037

GERP RS

-3.1

Varity_R

0.025

gMVP

0.025

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over