Variant 3-195779136-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_018406.7(MUC4):c.12444C>T(p.Thr4148Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000731 in 114,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00017 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MUC4
NM_018406.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.288

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 3-195779136-G-A is Benign according to our data. Variant chr3-195779136-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654383.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.288 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC4	NM_018406.7 linkuse as main transcript	c.12444C>T	p.Thr4148Thr	synonymous_variant	2/25	ENST00000463781.8	NP_060876.5	Q99102-1E9PDY6
MUC4	NM_004532.6 linkuse as main transcript	c.83-681C>T		intron_variant			NP_004523.3	Q99102-13A0T3F4
MUC4	NM_138297.5 linkuse as main transcript	c.83-4831C>T		intron_variant			NP_612154.2	Q99102-12A0T3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8 linkuse as main transcript	c.12444C>T	p.Thr4148Thr	synonymous_variant	2/25	5	NM_018406.7	ENSP00000417498.3		Q99102-1E9PDY6

Frequencies

GnomAD3 genomes

AF:

0.000731

AC:

AN:

114834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000595

Gnomad ASJ

AF:

0.000356

Gnomad EAS

AF:

0.000421

Gnomad SAS

AF:

0.000231

Gnomad FIN

AF:

0.000859

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000695

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.000577

AC:

AN:

147346

Hom.:

AF XY:

0.000525

AC XY:

AN XY:

78070

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.000377

Gnomad EAS exome

AF:

0.000188

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.00110

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000171

AC:

215

AN:

1259092

Hom.:

Cov.:

145

AF XY:

0.000187

AC XY:

116

AN XY:

621002

show subpopulations

Gnomad4 AFR exome

AF:

0.000612

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.000226

Gnomad4 EAS exome

AF:

0.000527

Gnomad4 SAS exome

AF:

0.000190

Gnomad4 FIN exome

AF:

0.000285

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000234

GnomAD4 genome

AF:

0.000731

AC:

AN:

114908

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

56614

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.000594

Gnomad4 ASJ

AF:

0.000356

Gnomad4 EAS

AF:

0.000422

Gnomad4 SAS

AF:

0.000231

Gnomad4 FIN

AF:

0.000859

Gnomad4 NFE

AF:

0.000695

Gnomad4 OTH

AF:

0.000662

Alfa

AF:

0.00329

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

MUC4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.7

DANN

Benign

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over