Variant 4-70481282-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152291.3(MUC7):c.538C>A(p.Pro180Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,782 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 32)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

MUC7
NM_152291.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

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:

MUC7 (HGNC:):

MUC7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05692911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC7	NM_152291.3 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	3/3	ENST00000304887.6	NP_689504.2	Q8TAX7
MUC7	NM_001145006.2 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	4/4		NP_001138478.1	Q8TAX7
MUC7	NM_001145007.2 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	4/4		NP_001138479.1	Q8TAX7
MUC7	XM_047415723.1 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	4/4		XP_047271679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUC7	ENST00000304887.6 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	3/3	1	NM_152291.3	ENSP00000302021.5	Q8TAX7
MUC7	ENST00000413702.5 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	4/4	4		ENSP00000407422.1	Q8TAX7
MUC7	ENST00000456088.5 linkuse as main transcript	c.538C>A	p.Pro180Thr	missense_variant	4/4	4		ENSP00000400585.1	Q8TAX7
MUC7	ENST00000514512.1 linkuse as main transcript	n.*4C>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250776

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS 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:

0.00000479

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 06, 2024

The c.538C>A (p.P180T) alteration is located in exon 4 (coding exon 2) of the MUC7 gene. This alteration results from a C to A substitution at nucleotide position 538, causing the proline (P) at amino acid position 180 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.59

DANN

Benign

0.28

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.45

T;.;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.071

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.017

B;B;B

Vest4

0.048

MutPred

0.30

Loss of glycosylation at P180 (P = 0.0034);Loss of glycosylation at P180 (P = 0.0034);Loss of glycosylation at P180 (P = 0.0034);

MVP

0.25

MPC

0.027

ClinPred

0.069

GERP RS

-4.8

Varity_R

0.041

gMVP

0.071

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over