4-70481100-C-A

Variant names:

• chr4-70481100-C-A
• rs899946185
• NM_152291.3:c.356C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152291.3(MUC7):​c.356C>A​(p.Ala119Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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]

ACMG classification

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=0.11234489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC7	NM_152291.3	c.356C>A	p.Ala119Asp	missense_variant	Exon 3 of 3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2	c.356C>A	p.Ala119Asp	missense_variant	Exon 4 of 4		NP_001138478.1
MUC7	NM_001145007.2	c.356C>A	p.Ala119Asp	missense_variant	Exon 4 of 4		NP_001138479.1
MUC7	XM_047415723.1	c.356C>A	p.Ala119Asp	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	c.356C>A	p.Ala119Asp	missense_variant	Exon 3 of 3	1	NM_152291.3	ENSP00000302021.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.40
DEOGEN2	Benign	0.025	T;.;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.39	T;T;.;.
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N;D;N;N
REVEL	Benign	0.079
Sift	Benign	0.088	T;D;T;T
Sift4G	Benign	0.39	T;D;T;T
Polyphen		0.95	P;.;P;P
Vest4		0.056
MutPred		0.20		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.54
MPC		0.14
ClinPred		0.28	T
GERP RS		1.4
Varity_R		0.13
gMVP		0.076

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

Other links and lift over

dbSNP: rs899946185; hg19: chr4-71346817;