Variant 6-30986501-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001010909.5(MUC21):c.326A>G(p.Glu109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 34)

Failed GnomAD Quality Control

Consequence

MUC21
NM_001010909.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.63

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051603585).

BP6

Variant 6-30986501-A-G is Benign according to our data. Variant chr6-30986501-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2559093.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC21	NM_001010909.5 linkuse as main transcript	c.326A>G	p.Glu109Gly	missense_variant	2/3	ENST00000376296.3	NP_001010909.2	Q5SSG8-1
MUC21	NR_130720.3 linkuse as main transcript	n.709A>G		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.326A>G	p.Glu109Gly	missense_variant	2/3	1	NM_001010909.5	ENSP00000365473.3		Q5SSG8-1
MUC21	ENST00000486149.2 linkuse as main transcript	c.-1037A>G		5_prime_UTR_variant	2/3	1		ENSP00000457640.1		A0A0C4DGM6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150762

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

168

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73640

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.010

DANN

Benign

0.44

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.27

M_CAP

Benign

0.0031

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.16

PROVEAN

Benign

-1.0

REVEL

Benign

0.017

Sift

Benign

0.18

Sift4G

Benign

0.27

Polyphen

0.0010

Vest4

0.050

MutPred

0.18

Gain of glycosylation at S108 (P = 0.0303);

MVP

0.014

MPC

0.16

ClinPred

0.059

GERP RS

-6.0

Varity_R

0.029

gMVP

0.041

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