rs6826961

chr4-70480984-C-Achr4-70480984-C-Gchr4-70480984-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152291.3(MUC7):c.240C>A(p.Asn80Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,768 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88

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 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=0.060606062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC7	NM_152291.3	c.240C>A	p.Asn80Lys	missense_variant	3/3	ENST00000304887.6
MUC7	NM_001145006.2	c.240C>A	p.Asn80Lys	missense_variant	4/4
MUC7	NM_001145007.2	c.240C>A	p.Asn80Lys	missense_variant	4/4
MUC7	XM_047415723.1	c.240C>A	p.Asn80Lys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC7	ENST00000304887.6	c.240C>A	p.Asn80Lys	missense_variant	3/3	1	NM_152291.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461768 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.021
Dann	Benign	0.14
DEOGEN2	Benign	0.010	T;.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00099	N
LIST_S2	Benign	0.32	T;T;.;.
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.061	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;.;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.51	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0060	B;.;B;B
Vest4		0.016
MutPred		0.13		Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);Gain of methylation at N80 (P = 0.0021);
MVP		0.19
MPC		0.060
ClinPred		0.037	T
GERP RS		-3.1
Varity_R		0.025
gMVP		0.025

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: rs6826961; hg19: chr4-71346701;