3-195752385-T-G

Variant names:

• chr3-195752385-T-G
• rs2258447
• NM_018406.7:c.15570A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018406.7(MUC4):​c.15570A>C​(p.Glu5190Asp) 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. 15/20 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: 34)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 31 publications found

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022405714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018406.7. 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
	MUC4	NM_018406.7	MANE Select	c.15570A>C	p.Glu5190Asp	missense	Exon 21 of 25	NP_060876.5
	MUC4	NM_004532.6		c.2862A>C	p.Glu954Asp	missense	Exon 20 of 24	NP_004523.3
	MUC4	NM_138297.5		c.2709A>C	p.Glu903Asp	missense	Exon 19 of 23	NP_612154.2	Q99102-12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.15570A>C	p.Glu5190Asp	missense	Exon 21 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.2862A>C	p.Glu954Asp	missense	Exon 20 of 24	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.2709A>C	p.Glu903Asp	missense	Exon 19 of 23	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.039
DANN	Benign	0.32
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.036
MutPred		0.36		Loss of disorder (P = 0.1365)
MVP		0.014
ClinPred		0.053	T
GERP RS		-9.5
gMVP		0.57
Mutation Taster		=91/9	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: rs2258447; hg19: chr3-195479256;