chr3-195790682-A-C

Variant names:

• chr3-195790682-A-C
• rs882605
• NM_018406.7:c.898T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018406.7(MUC4):​c.898T>G​(p.Phe300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,774 control chromosomes in the GnomAD database, including 527,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.80 (49061 hom., cov: 31)
  • Exomes 𝑓: 0.81 (478365 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 43 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1403313E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

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.898T>G	p.Phe300Val	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-12227T>G		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-16377T>G		intron	N/A	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.898T>G	p.Phe300Val	missense	Exon 2 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.83-12227T>G		intron	N/A	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.83-16377T>G		intron	N/A	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121801 AN: 151982 Hom.: 49024 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.824

GnomAD2 exomes AF: 0.776 AC: 193245 AN: 249178 AF XY: 0.776

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.806

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.807 AC: 1179675 AN: 1461674 Hom.: 478365 Cov.: 69 AF XY: 0.804 AC XY: 584472 AN XY: 727126

African (AFR) AF: 0.815 AC: 27289 AN: 33480

American (AMR) AF: 0.638 AC: 28552 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 22169 AN: 26136

East Asian (EAS) AF: 0.813 AC: 32285 AN: 39700

South Asian (SAS) AF: 0.669 AC: 57665 AN: 86256

European-Finnish (FIN) AF: 0.792 AC: 42283 AN: 53402

Middle Eastern (MID) AF: 0.813 AC: 4688 AN: 5768

European-Non Finnish (NFE) AF: 0.824 AC: 915742 AN: 1111834

Other (OTH) AF: 0.812 AC: 49002 AN: 60374

GnomAD4 genome AF: 0.801 AC: 121886 AN: 152100 Hom.: 49061 Cov.: 31 AF XY: 0.797 AC XY: 59261 AN XY: 74338

African (AFR) AF: 0.816 AC: 33839 AN: 41484

American (AMR) AF: 0.713 AC: 10905 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4143 AN: 5168

South Asian (SAS) AF: 0.677 AC: 3255 AN: 4806

European-Finnish (FIN) AF: 0.802 AC: 8481 AN: 10574

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55650 AN: 67994

Other (OTH) AF: 0.826 AC: 1744 AN: 2112

Alfa AF: 0.820 Hom.: 151344

Bravo AF: 0.796

TwinsUK AF: 0.826 AC: 3064

ALSPAC AF: 0.824 AC: 3175

ESP6500AA AF: 0.829 AC: 3311

ESP6500EA AF: 0.825 AC: 6880

ExAC AF: 0.781 AC: 94339

Asia WGS AF: 0.807 AC: 2809 AN: 3478

EpiCase AF: 0.833

EpiControl AF: 0.839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.012
DANN	Benign	0.50
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00077	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Vest4		0.072
ClinPred		0.0037	T
GERP RS		-7.1
gMVP		0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs882605; hg19: chr3-195517553; COSMIC: COSV62205739;