chr4-70481282-C-T

Variant names:

• chr4-70481282-C-T
• rs764283926
• NM_152291.3:c.538C>T

Variant summary

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

The NM_152291.3(MUC7):​c.538C>T​(p.Pro180Ser) 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: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=0.07378769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC7	NM_152291.3	c.538C>T	p.Pro180Ser	missense_variant	Exon 3 of 3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2	c.538C>T	p.Pro180Ser	missense_variant	Exon 4 of 4		NP_001138478.1
MUC7	NM_001145007.2	c.538C>T	p.Pro180Ser	missense_variant	Exon 4 of 4		NP_001138479.1
MUC7	XM_047415723.1	c.538C>T	p.Pro180Ser	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.538C>T	p.Pro180Ser	missense_variant	Exon 3 of 3	1	NM_152291.3	ENSP00000302021.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151690 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151808 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74220

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.65
DANN	Benign	0.51
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.40	T;.;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.028
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.095	B;B;B
Vest4		0.075
MutPred		0.32		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		0.26
MPC		0.025
ClinPred		0.056	T
GERP RS		-4.8
Varity_R		0.035
gMVP		0.064

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: rs764283926; hg19: chr4-71346999;