NM_152291.3:c.655C>T

Variant names:

• chr4-70481399-C-T
• rs41454651
• NM_152291.3:c.655C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_152291.3(MUC7):​c.655C>T​(p.Pro219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 117,010 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.50
• Publications: 5 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064270794).
• BP6: Variant 4-70481399-C-T is Benign according to our data. Variant chr4-70481399-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3150682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.655C>T	p.Pro219Ser	missense	Exon 3 of 3	NP_689504.2	Q8TAX7
	MUC7	NM_001145006.2		c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	NP_001138478.1	Q8TAX7
	MUC7	NM_001145007.2		c.655C>T	p.Pro219Ser	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.655C>T	p.Pro219Ser	missense	Exon 3 of 3	ENSP00000302021.5	Q8TAX7
	MUC7	ENST00000413702.5	TSL:4	c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	ENSP00000407422.1	Q8TAX7
	MUC7	ENST00000456088.5	TSL:4	c.655C>T	p.Pro219Ser	missense	Exon 4 of 4	ENSP00000400585.1	Q8TAX7

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 364 AN: 116956 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000766

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00467

Gnomad NFE AF: 0.0000352

Gnomad OTH AF: 0.00246

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 241052 AF XY: 0.00

Gnomad AFR exome AF: 0.0000658

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1419724 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 706118

African (AFR) AF: 0.00 AC: 0 AN: 30912

American (AMR) AF: 0.00 AC: 0 AN: 43222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24642

East Asian (EAS) AF: 0.00 AC: 0 AN: 37968

South Asian (SAS) AF: 0.00 AC: 0 AN: 85832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083304

Other (OTH) AF: 0.00 AC: 0 AN: 57076

GnomAD4 genome AF: 0.00313 AC: 366 AN: 117010 Hom.: 2 Cov.: 26 AF XY: 0.00343 AC XY: 195 AN XY: 56796

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0119 AC: 344 AN: 28918

American (AMR) AF: 0.00106 AC: 12 AN: 11306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2990

East Asian (EAS) AF: 0.000769 AC: 3 AN: 3902

South Asian (SAS) AF: 0.00 AC: 0 AN: 3418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7110

Middle Eastern (MID) AF: 0.00515 AC: 1 AN: 194

European-Non Finnish (NFE) AF: 0.0000352 AC: 2 AN: 56828

Other (OTH) AF: 0.00244 AC: 4 AN: 1642

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00989 Hom.: 9

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0030
DANN	Benign	0.11
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-4.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.035
Sift	Benign	0.98	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.093
MVP		0.17
MPC		0.025
ClinPred		0.035	T
GERP RS		-3.8
Varity_R		0.016
gMVP		0.037
Mutation Taster		=100/0	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: rs41454651; hg19: chr4-71347116; COSMIC: COSV59217029; COSMIC: COSV59217029;