4-70480821-A-G

Variant summary

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

The NM_152291.3(MUC7):ā€‹c.77A>Gā€‹(p.Asp26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MUC7
NM_152291.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.681
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]

Genome browser will be placed here

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=0.04522538).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUC7NM_152291.3 linkuse as main transcriptc.77A>G p.Asp26Gly missense_variant 3/3 ENST00000304887.6 NP_689504.2
MUC7NM_001145006.2 linkuse as main transcriptc.77A>G p.Asp26Gly missense_variant 4/4 NP_001138478.1
MUC7NM_001145007.2 linkuse as main transcriptc.77A>G p.Asp26Gly missense_variant 4/4 NP_001138479.1
MUC7XM_047415723.1 linkuse as main transcriptc.77A>G p.Asp26Gly missense_variant 4/4 XP_047271679.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUC7ENST00000304887.6 linkuse as main transcriptc.77A>G p.Asp26Gly missense_variant 3/31 NM_152291.3 ENSP00000302021 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461558
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsApr 09, 2024The c.77A>G (p.D26G) alteration is located in exon 4 (coding exon 2) of the MUC7 gene. This alteration results from a A to G substitution at nucleotide position 77, causing the aspartic acid (D) at amino acid position 26 to be replaced by a glycine (G). 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
0.18
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.073
DANN
Benign
0.24
DEOGEN2
Benign
0.013
T;.;T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.34
T;T;.;.
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.045
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;.;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.0
N;N;N;N
REVEL
Benign
0.013
Sift
Benign
0.50
T;T;T;T
Sift4G
Benign
0.50
T;T;T;T
Polyphen
0.016
B;.;B;B
Vest4
0.053
MutPred
0.19
Loss of stability (P = 0.037);Loss of stability (P = 0.037);Loss of stability (P = 0.037);Loss of stability (P = 0.037);
MVP
0.18
MPC
0.029
ClinPred
0.035
T
GERP RS
-2.0
Varity_R
0.028
gMVP
0.072

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.

Other links and lift over

dbSNP: rs368454838; hg19: chr4-71346538; API