NM_152291.3:c.548C>T

Variant names:

• chr4-70481292-C-T
• rs781715844
• NM_152291.3:c.548C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_152291.3(MUC7):​c.548C>T​(p.Ser183Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM1: In a glycosylation_site O-linked (GalNAc) serine; by GALNT13 (size 0) in uniprot entity MUC7_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.17618397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC7	NM_152291.3	MANE Select	c.548C>T	p.Ser183Leu	missense	Exon 3 of 3	NP_689504.2	Q8TAX7
	MUC7	NM_001145006.2		c.548C>T	p.Ser183Leu	missense	Exon 4 of 4	NP_001138478.1	Q8TAX7
	MUC7	NM_001145007.2		c.548C>T	p.Ser183Leu	missense	Exon 4 of 4	NP_001138479.1	Q8TAX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC7	ENST00000304887.6	TSL:1 MANE Select	c.548C>T	p.Ser183Leu	missense	Exon 3 of 3	ENSP00000302021.5	Q8TAX7
	MUC7	ENST00000413702.5	TSL:4	c.548C>T	p.Ser183Leu	missense	Exon 4 of 4	ENSP00000407422.1	Q8TAX7
	MUC7	ENST00000456088.5	TSL:4	c.548C>T	p.Ser183Leu	missense	Exon 4 of 4	ENSP00000400585.1	Q8TAX7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251168 AF XY: 0.0000295

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461754 Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.096
Sift	Benign	0.062	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.88	P
Vest4		0.088
MVP		0.48
MPC		0.024
ClinPred		0.33	T
GERP RS		1.6
Varity_R		0.065
gMVP		0.072
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs781715844; hg19: chr4-71347009;