3-195779220-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_018406.7(MUC4):​c.12360T>A​(p.Ser4120Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). 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
• 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: Benign. The variant received -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

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>A	p.Ser4120Ser	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-765T>A		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-4915T>A		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>A	p.Ser4120Ser	synonymous	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-765T>A		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-4915T>A		intron	N/A	ENSP00000338109.4

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

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

African (AFR) AF: 0.0426 AC: 593 AN: 13906

American (AMR) AF: 0.0873 AC: 1435 AN: 16446

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 667 AN: 9606

East Asian (EAS) AF: 0.150 AC: 1509 AN: 10054

South Asian (SAS) AF: 0.0434 AC: 1772 AN: 40862

European-Finnish (FIN) AF: 0.0386 AC: 735 AN: 19044

Middle Eastern (MID) AF: 0.0240 AC: 47 AN: 1958

European-Non Finnish (NFE) AF: 0.0314 AC: 17982 AN: 572058

Other (OTH) AF: 0.0408 AC: 1106 AN: 27078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.00940 AC: 146 AN: 15532

American (AMR) AF: 0.00270 AC: 19 AN: 7038

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 4 AN: 1766

East Asian (EAS) AF: 0.00651 AC: 13 AN: 1996

South Asian (SAS) AF: 0.00734 AC: 15 AN: 2044

European-Finnish (FIN) AF: 0.00552 AC: 26 AN: 4714

Middle Eastern (MID) AF: 0.0395 AC: 3 AN: 76

European-Non Finnish (NFE) AF: 0.00303 AC: 102 AN: 33676

Other (OTH) AF: 0.00438 AC: 4 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	1.4
DANN	Benign	0.17
PhyloP100		-0.20
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: rs74941663; hg19: chr3-195506091; COSMIC: COSV57794636; COSMIC: COSV57794636;