3-195762232-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.14367C>T(p.Thr4789=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,588,344 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.985

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=-0.83).
• BP6: Variant 3-195762232-G-A is Benign according to our data. Variant chr3-195762232-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.985 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.14367C>T	p.Thr4789=	synonymous_variant	14/25	ENST00000463781.8
MUC4	NM_004532.6	c.1659C>T	p.Thr553=	synonymous_variant	13/24
MUC4	NM_138297.5	c.1506C>T	p.Thr502=	synonymous_variant	12/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.14367C>T	p.Thr4789=	synonymous_variant	14/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152136 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00240 AC: 479 AN: 199436 Hom.: 4 AF XY: 0.00237 AC XY: 256 AN XY: 107898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000662

Gnomad ASJ exome AF: 0.0452

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000625

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00116 AC: 1669 AN: 1436208 Hom.: 24 Cov.: 35 AF XY: 0.00119 AC XY: 848 AN XY: 712018

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.0000242

Gnomad4 ASJ exome AF: 0.0485

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.00143 AC: 217 AN: 152136 Hom.: 7 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74308

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.00390 Hom.: 3

Bravo AF: 0.00139

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

Mar 01, 2022

MUC4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.31
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141301810; hg19: chr3-195489103; COSMIC: COSV104611664; COSMIC: COSV104611664;