3-195779220-A-T

Position:

• chr3-195779220-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_018406.7(MUC4):​c.12360T>A​(p.Ser4120=) 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. Synonymous variant affecting the same amino acid position (i.e. S4120S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 10)
  • Exomes 𝑓: 0.036 (4494 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.12).
• BP7: Synonymous conserved (PhyloP=-0.203 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12360T>A	p.Ser4120=	synonymous_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-765T>A		intron_variant
MUC4	NM_138297.5	c.83-4915T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12360T>A	p.Ser4120=	synonymous_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 332 AN: 68036 Hom.: 3 Cov.: 10

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.00292

Gnomad AMR AF: 0.00270

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00651

Gnomad SAS AF: 0.00736

Gnomad FIN AF: 0.00552

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00442

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0364 AC: 25846 AN: 711012 Hom.: 4494 Cov.: 52 AF XY: 0.0388 AC XY: 13550 AN XY: 349078

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0873

Gnomad4 ASJ exome AF: 0.0694

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.0386

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0408

GnomAD4 genome AF: 0.00489 AC: 333 AN: 68098 Hom.: 3 Cov.: 10 AF XY: 0.00492 AC XY: 164 AN XY: 33350

Gnomad4 AFR AF: 0.00940

Gnomad4 AMR AF: 0.00270

Gnomad4 ASJ AF: 0.00227

Gnomad4 EAS AF: 0.00651

Gnomad4 SAS AF: 0.00734

Gnomad4 FIN AF: 0.00552

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.17

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

LitVar

Other links and lift over

dbSNP: rs74941663; hg19: chr3-195506091; COSMIC: COSV57794636; COSMIC: COSV57794636;