4-70480979-A-C

Variant names:

• chr4-70480979-A-C
• rs776332319
• NM_152291.3:c.235A>C

Variant summary

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

The NM_152291.3(MUC7):​c.235A>C​(p.Asn79His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,828 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=0.05989921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC7	NM_152291.3	c.235A>C	p.Asn79His	missense_variant	Exon 3 of 3	ENST00000304887.6	NP_689504.2
MUC7	NM_001145006.2	c.235A>C	p.Asn79His	missense_variant	Exon 4 of 4		NP_001138478.1
MUC7	NM_001145007.2	c.235A>C	p.Asn79His	missense_variant	Exon 4 of 4		NP_001138479.1
MUC7	XM_047415723.1	c.235A>C	p.Asn79His	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.235A>C	p.Asn79His	missense_variant	Exon 3 of 3	1	NM_152291.3	ENSP00000302021.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251276 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135796

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: 0.00000274 AC: 4 AN: 1461828 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727218

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.046
DANN	Benign	0.15
DEOGEN2	Benign	0.014	T;.;T;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.31	T;T;.;.
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.060	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.39	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.099
MutPred		0.21		Loss of glycosylation at P82 (P = 0.0075);Loss of glycosylation at P82 (P = 0.0075);Loss of glycosylation at P82 (P = 0.0075);Loss of glycosylation at P82 (P = 0.0075);
MVP		0.25
MPC		0.026
ClinPred		0.033	T
GERP RS		-4.8
Varity_R		0.032
gMVP		0.033

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: rs776332319; hg19: chr4-71346696;