rs199812923

chr3-195783357-C-Achr3-195783357-C-Gchr3-195783357-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_018406.7(MUC4):c.8223G>T(p.Glu2741Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.020 (50 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008604169).
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0196 (6361/323824) while in subpopulation AFR AF= 0.0408 (483/11826). AF 95% confidence interval is 0.0378. There are 50 homozygotes in gnomad4_exome. There are 3189 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.8223G>T	p.Glu2741Asp	missense_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-4902G>T		intron_variant
MUC4	NM_138297.5	c.83-9052G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.8223G>T	p.Glu2741Asp	missense_variant	2/25	5	NM_018406.7	A2

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 29 AN: 9372 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00314

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00103 AC: 47 AN: 45466 Hom.: 0 AF XY: 0.00114 AC XY: 27 AN XY: 23748

Gnomad AFR exome AF: 0.000454

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.000987

Gnomad EAS exome AF: 0.000833

Gnomad SAS exome AF: 0.000811

Gnomad FIN exome AF: 0.000260

Gnomad NFE exome AF: 0.00138

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.0196 AC: 6361 AN: 323824 Hom.: 50 Cov.: 8 AF XY: 0.0198 AC XY: 3189 AN XY: 160996

Gnomad4 AFR exome AF: 0.0408

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.00427

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.00604

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.00330 AC: 31 AN: 9384 Hom.: 0 Cov.: 0 AF XY: 0.00428 AC XY: 19 AN XY: 4436

Gnomad4 AFR AF: 0.00808

Gnomad4 AMR AF: 0.00139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00316

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00

ExAC AF: 0.000104 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.18
Dann	Benign	0.31
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.0060
Sift	Benign	1.0	T;T
Sift4G	Benign	0.54	T;T
Vest4		0.047
MVP		0.014
ClinPred		0.0038	T
GERP RS		-1.4
gMVP		0.000053

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

LitVar

Other links and lift over

dbSNP: rs199812923; hg19: chr3-195510228;