dbSNP rs772843697: MUC21:p.Ala222ValfsTer221 (chr6-30986839-GC-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001010909.5(MUC21):c.665delC(p.Ala222ValfsTer221) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 144,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC21
NM_001010909.5 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 6-30986839-GC-G is Benign according to our data. Variant chr6-30986839-GC-G is described in ClinVar as [Benign]. Clinvar id is 243064.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC21	NM_001010909.5 link	c.665delC	p.Ala222ValfsTer221	frameshift_variant	Exon 2 of 3	ENST00000376296.3	NP_001010909.2	Q5SSG8-1
MUC21	NR_130720.3 link	n.1048delC		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC21	ENST00000376296.3 link	c.665delC	p.Ala222ValfsTer221	frameshift_variant	Exon 2 of 3	1	NM_001010909.5	ENSP00000365473.3		Q5SSG8-1
MUC21	ENST00000486149 link	c.-698delC		5_prime_UTR_variant	Exon 2 of 3	1		ENSP00000457640.1		A0A0C4DGM6

Frequencies

GnomAD3 genomes

AF:

0.0000621

AC:

AN:

144824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000121

Gnomad OTH

AF:

0.000508

GnomAD3 exomes

AF:

0.000136

AC:

AN:

250912

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000138

AC:

199

AN:

1437852

Hom.:

Cov.:

180

AF XY:

0.000138

AC XY:

AN XY:

715034

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000958

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000621

AC:

AN:

144824

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

70476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000121

Gnomad4 OTH

AF:

0.000508

Alfa

AF:

0.000169

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 01, 2015

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Benign. This variant was found to be outside the region (chr6:32557483-35479574) linked to juvenile cataracts using SNP-based fine mapping. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over