chr3-195783357-C-T

Variant names:

• chr3-195783357-C-T
• rs199812923
• NM_018406.7:c.8223G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_018406.7(MUC4):​c.8223G>A​(p.Glu2741Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 10 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.8223G>A	p.Glu2741Glu	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-4902G>A		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-9052G>A		intron	N/A	NP_612154.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.8223G>A	p.Glu2741Glu	synonymous	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-4902G>A		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-9052G>A		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 9402 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 333476 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 165828

African (AFR) AF: 0.00 AC: 0 AN: 12402

American (AMR) AF: 0.00 AC: 0 AN: 7904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5940

East Asian (EAS) AF: 0.00 AC: 0 AN: 9420

South Asian (SAS) AF: 0.00 AC: 0 AN: 20922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 251754

Other (OTH) AF: 0.00 AC: 0 AN: 14168

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 9402 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4438

African (AFR) AF: 0.00 AC: 0 AN: 2850

American (AMR) AF: 0.00 AC: 0 AN: 726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 338

East Asian (EAS) AF: 0.00 AC: 0 AN: 318

South Asian (SAS) AF: 0.00 AC: 0 AN: 132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4302

Other (OTH) AF: 0.00 AC: 0 AN: 132

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.18
PhyloP100		-3.5

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: rs199812923; hg19: chr3-195510228;