Genetic Variant NM_018406.7:c.12360T>A (chr3-195779220-A-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

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. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203

Publications

5 publications found

Variant links:

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]

MUC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7 link	c.12360T>A	p.Ser4120Ser	synonymous_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 link	c.83-765T>A		intron_variant	Intron 1 of 23		NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 link	c.83-4915T>A		intron_variant	Intron 1 of 22		NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 link	c.12360T>A	p.Ser4120Ser	synonymous_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

332

AN:

68036

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0388

AC XY:

13550

AN XY:

349078

show subpopulations

⚠️ 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:

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 = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.347

Heterozygous variant carriers

1317

2634

3952

5269

6586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00489

AC:

333

AN:

68098

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

164

AN XY:

33350

show subpopulations

⚠️ 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:

AN:

7038

Ashkenazi Jewish (ASJ)

AF:

0.00227

AC:

AN:

1766

East Asian (EAS)

AF:

0.00651

AC:

AN:

1996

South Asian (SAS)

AF:

0.00734

AC:

AN:

2044

European-Finnish (FIN)

AF:

0.00552

AC:

AN:

4714

Middle Eastern (MID)

AF:

0.0395

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00303

AC:

102

AN:

33676

Other (OTH)

AF:

0.00438

AC:

AN:

914

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.295

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

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

(source)

DANN

Benign

0.17

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over