3-195779220-A-G

Variant names:

• chr3-195779220-A-G
• rs74941663
• NM_018406.7:c.12360T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018406.7(MUC4):​c.12360T>C​(p.Ser4120Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 837,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S4120S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 10)
  • Exomes 𝑓: 0.0000026 (1 hom.)
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 5 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP7: Synonymous conserved (PhyloP=-0.203 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.12360T>C	p.Ser4120Ser	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-765T>C		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-4915T>C		intron	N/A	NP_612154.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.12360T>C	p.Ser4120Ser	synonymous	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-765T>C		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-4915T>C		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.0000146 AC: 1 AN: 68704 Hom.: 0 Cov.: 10

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: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000260 AC: 2 AN: 768892 Hom.: 1 Cov.: 52 AF XY: 0.00000530 AC XY: 2 AN XY: 377244

African (AFR) AF: 0.00 AC: 0 AN: 14804

American (AMR) AF: 0.00 AC: 0 AN: 17738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10604

East Asian (EAS) AF: 0.00 AC: 0 AN: 11166

South Asian (SAS) AF: 0.00 AC: 0 AN: 43434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2058

European-Non Finnish (NFE) AF: 0.00000323 AC: 2 AN: 619804

Other (OTH) AF: 0.00 AC: 0 AN: 29266

GnomAD4 genome AF: 0.0000146 AC: 1 AN: 68704 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 33594

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

African (AFR) AF: 0.00 AC: 0 AN: 15728

American (AMR) AF: 0.00 AC: 0 AN: 7082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1784

East Asian (EAS) AF: 0.00 AC: 0 AN: 2018

South Asian (SAS) AF: 0.00 AC: 0 AN: 2060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 80

European-Non Finnish (NFE) AF: 0.0000295 AC: 1 AN: 33946

Other (OTH) AF: 0.00 AC: 0 AN: 914

⚠️ 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: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.0
DANN	Benign	0.23
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs74941663; hg19: chr3-195506091;