rs9295938

Positions:

• chr6-30985328-G-A
• chr6-30985328-G-T

Variant summary

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

The NM_001010909.5(MUC21):​c.62-909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,148 control chromosomes in the GnomAD database, including 1,453 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 0.12 (1453 hom., cov: 32)
• Consequence: MUC21 NM_001010909.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

MUC21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC21	NM_001010909.5	c.62-909G>A		intron_variant		ENST00000376296.3	NP_001010909.2
MUC21	NR_130720.3	n.445-909G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC21	ENST00000376296.3	c.62-909G>A		intron_variant		1	NM_001010909.5	ENSP00000365473.3
MUC21	ENST00000486149.2	c.-1301-909G>A		intron_variant		1		ENSP00000457640.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19020 AN: 152028 Hom.: 1455 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19016 AN: 152148 Hom.: 1453 Cov.: 32 AF XY: 0.127 AC XY: 9442 AN XY: 74386

Gnomad4 AFR AF: 0.0686

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.117

Alfa AF: 0.127 Hom.: 667

Bravo AF: 0.119

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.66

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: rs9295938; hg19: chr6-30953105;