Variant 6-30986703-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001010909.5(MUC21):c.528G>A(p.Gly176Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 113,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC21
NM_001010909.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.65

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:

MUC21 (HGNC:):

MUC21 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-30986703-G-A is Benign according to our data. Variant chr6-30986703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656353.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC21	NM_001010909.5 linkuse as main transcript	c.528G>A	p.Gly176Gly	synonymous_variant	2/3	ENST00000376296.3	NP_001010909.2	Q5SSG8-1
MUC21	NR_130720.3 linkuse as main transcript	n.911G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC21	ENST00000376296.3 linkuse as main transcript	c.528G>A	p.Gly176Gly	synonymous_variant	2/3	1	NM_001010909.5	ENSP00000365473.3		Q5SSG8-1
MUC21	ENST00000486149.2 linkuse as main transcript	c.-835G>A		5_prime_UTR_variant	2/3	1		ENSP00000457640.1		A0A0C4DGM6

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

119

AN:

113538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00130

Gnomad ASJ

AF:

0.00400

Gnomad EAS

AF:

0.000485

Gnomad SAS

AF:

0.00130

Gnomad FIN

AF:

0.000347

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00114

Gnomad OTH

AF:

0.00266

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000326

AC:

AN:

1225358

Hom.:

Cov.:

165

AF XY:

0.0000312

AC XY:

AN XY:

608814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000364

Gnomad4 AMR exome

AF:

0.0000879

Gnomad4 ASJ exome

AF:

0.000213

Gnomad4 EAS exome

AF:

0.0000933

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000266

Gnomad4 OTH exome

AF:

0.0000596

GnomAD4 genome

AF:

0.00107

AC:

122

AN:

113628

Hom.:

Cov.:

AF XY:

0.000917

AC XY:

AN XY:

55640

show subpopulations

Gnomad4 AFR

AF:

0.000892

Gnomad4 AMR

AF:

0.00130

Gnomad4 ASJ

AF:

0.00400

Gnomad4 EAS

AF:

0.000486

Gnomad4 SAS

AF:

0.00130

Gnomad4 FIN

AF:

0.000347

Gnomad4 NFE

AF:

0.00114

Gnomad4 OTH

AF:

0.00264

Alfa

AF:

0.0937

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

MUC21: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

DANN

Benign

0.42

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