4-70480950-G-T

Position:

• chr4-70480950-G-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.206G>T​(p.Arg69Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MUC7 NM_152291.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.39

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=0.049512714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC7	NM_152291.3	c.206G>T	p.Arg69Leu	missense_variant	3/3	ENST00000304887.6
MUC7	NM_001145006.2	c.206G>T	p.Arg69Leu	missense_variant	4/4
MUC7	NM_001145007.2	c.206G>T	p.Arg69Leu	missense_variant	4/4
MUC7	XM_047415723.1	c.206G>T	p.Arg69Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC7	ENST00000304887.6	c.206G>T	p.Arg69Leu	missense_variant	3/3	1	NM_152291.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.206G>T (p.R69L) alteration is located in exon 4 (coding exon 2) of the MUC7 gene. This alteration results from a G to T substitution at nucleotide position 206, causing the arginine (R) at amino acid position 69 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.054
DANN	Benign	0.77
DEOGEN2	Benign	0.019	T;.;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.52	T;T;.;.
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.66	N;D;N;N
REVEL	Benign	0.022
Sift	Benign	0.079	T;D;T;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.099	B;.;B;B
Vest4		0.11
MutPred		0.24		Loss of glycosylation at P72 (P = 0.0079);Loss of glycosylation at P72 (P = 0.0079);Loss of glycosylation at P72 (P = 0.0079);Loss of glycosylation at P72 (P = 0.0079);
MVP		0.19
MPC		0.047
ClinPred		0.094	T
GERP RS		-6.1
Varity_R		0.045
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-71346667;