Variant 4-70481038-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152291.3(MUC7):c.294C>A(p.Ser98Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,836 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 1 hom. )

Consequence

MUC7
NM_152291.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.144

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073099315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MUC7	NM_152291.3 linkuse as main transcript	c.294C>A	p.Ser98Arg	missense_variant	3/3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2 linkuse as main transcript	c.294C>A	p.Ser98Arg	missense_variant	4/4		NP_001138478.1
MUC7	NM_001145007.2 linkuse as main transcript	c.294C>A	p.Ser98Arg	missense_variant	4/4		NP_001138479.1
MUC7	XM_047415723.1 linkuse as main transcript	c.294C>A	p.Ser98Arg	missense_variant	4/4		XP_047271679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC7	ENST00000304887.6 linkuse as main transcript	c.294C>A	p.Ser98Arg	missense_variant	3/3	1	NM_152291.3	ENSP00000302021	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251104

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135696

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 SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 15, 2023

The c.294C>A (p.S98R) 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 294, causing the serine (S) at amino acid position 98 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.016

T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.26

T;T;.;.

M_CAP

Benign

0.0029

MetaRNN

Benign

0.073

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.058

T;T;T;T

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.12

B;.;B;B

Vest4

0.13

MutPred

0.24

Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);

MVP

0.32

MPC

0.037

ClinPred

0.049

GERP RS

0.59

Varity_R

0.072

gMVP

0.057

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