rs886403

Positions:

• chr6-30989841-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010909.5(MUC21):​c.*1647T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,178 control chromosomes in the GnomAD database, including 4,271 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4271 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: MUC21 NM_001010909.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

MUC21 (HGNC:21661): (mucin 21, cell surface associated) This gene encodes a large membrane-bound glycoprotein which is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. The encoded protein contains an N-terminal signal sequence, an extracellular mucin domain, a stem domain, a transmembrane domain, and a C-terminal cytoplasmic tail domain. The mucin domain contains O-glycosylation sites and is polymorphic with isoforms containing a variable number of nonidentical proline-, threonine-, and serine-rich tandem repeats of 15 amino acids each. The aberrent expression of this gene is associated with lung adenocarcinoma. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC21	NM_001010909.5	c.*1647T>C		3_prime_UTR_variant	3/3	ENST00000376296.3
MUC21	NR_130720.3	n.3731T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC21	ENST00000376296.3	c.*1647T>C		3_prime_UTR_variant	3/3	1	NM_001010909.5	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34021 AN: 152052 Hom.: 4272 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.224 AC: 34027 AN: 152170 Hom.: 4271 Cov.: 32 AF XY: 0.216 AC XY: 16080 AN XY: 74410

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.241

Alfa AF: 0.277 Hom.: 3050

Bravo AF: 0.228

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.48

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: rs886403; hg19: chr6-30957618;