3-195779220-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018406.7(MUC4):​c.12360T>G​(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 Benign (★). Synonymous variant affecting the same amino acid position (i.e. S4120S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.45 (5448 hom., cov: 10)
  • Exomes 𝑓: 0.24 (31935 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.16).
• BP6: Variant 3-195779220-A-C is Benign according to our data. Variant chr3-195779220-A-C is described in ClinVar as Benign. ClinVar VariationId is 403118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.203 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5448 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>G	p.Ser4120Ser	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-765T>G		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-4915T>G		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>G	p.Ser4120Ser	synonymous	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-765T>G		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-4915T>G		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.447 AC: 28242 AN: 63226 Hom.: 5444 Cov.: 10

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.455

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.236 AC: 140416 AN: 596116 Hom.: 31935 Cov.: 52 AF XY: 0.229 AC XY: 67432 AN XY: 294936

African (AFR) AF: 0.220 AC: 2633 AN: 11966

American (AMR) AF: 0.107 AC: 1798 AN: 16734

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 2724 AN: 9006

East Asian (EAS) AF: 0.217 AC: 2202 AN: 10170

South Asian (SAS) AF: 0.134 AC: 4933 AN: 36688

European-Finnish (FIN) AF: 0.232 AC: 3989 AN: 17182

Middle Eastern (MID) AF: 0.178 AC: 316 AN: 1778

European-Non Finnish (NFE) AF: 0.248 AC: 116272 AN: 469072

Other (OTH) AF: 0.236 AC: 5549 AN: 23520

GnomAD4 genome AF: 0.447 AC: 28261 AN: 63292 Hom.: 5448 Cov.: 10 AF XY: 0.444 AC XY: 13769 AN XY: 31002

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

African (AFR) AF: 0.345 AC: 4729 AN: 13698

American (AMR) AF: 0.420 AC: 2762 AN: 6580

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 979 AN: 1676

East Asian (EAS) AF: 0.623 AC: 1200 AN: 1926

South Asian (SAS) AF: 0.431 AC: 843 AN: 1958

European-Finnish (FIN) AF: 0.505 AC: 2280 AN: 4514

Middle Eastern (MID) AF: 0.308 AC: 24 AN: 78

European-Non Finnish (NFE) AF: 0.470 AC: 14891 AN: 31662

Other (OTH) AF: 0.460 AC: 402 AN: 874

⚠️ 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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	1.5
DANN	Benign	0.20
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: COSV57778184; COSMIC: COSV57778184;