3-195779136-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018406.7(MUC4):c.12444C>T(p.Thr4148=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288

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 -11 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.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.12444C>T	p.Thr4148=	synonymous_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-681C>T		intron_variant
MUC4	NM_138297.5	c.83-4831C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.12444C>T	p.Thr4148=	synonymous_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.000731 AC: 84 AN: 114834 Hom.: 0 Cov.: 23

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: 85 AN: 147346 Hom.: 3 AF XY: 0.000525 AC XY: 41 AN XY: 78070

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.: 1 Cov.: 145 AF XY: 0.000187 AC XY: 116 AN XY: 621002

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: 84 AN: 114908 Hom.: 0 Cov.: 23 AF XY: 0.000565 AC XY: 32 AN XY: 56614

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs200261480; hg19: chr3-195506007; COSMIC: COSV57779974; COSMIC: COSV57779974;