Variant 6-30986478-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001010909.5(MUC21):c.303G>A(p.Gly101Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,599,330 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0018 ( 22 hom. )

Consequence

MUC21
NM_001010909.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 6-30986478-G-A is Benign according to our data. Variant chr6-30986478-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656348.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00178 (2581/1447616) while in subpopulation MID AF= 0.0287 (163/5678). AF 95% confidence interval is 0.0251. There are 22 homozygotes in gnomad4_exome. There are 1349 alleles in male gnomad4_exome subpopulation. Median coverage is 166. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC21	NM_001010909.5 linkuse as main transcript	c.303G>A	p.Gly101Gly	synonymous_variant	2/3	ENST00000376296.3	NP_001010909.2	Q5SSG8-1
MUC21	NR_130720.3 linkuse as main transcript	n.686G>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.303G>A	p.Gly101Gly	synonymous_variant	2/3	1	NM_001010909.5	ENSP00000365473.3		Q5SSG8-1
MUC21	ENST00000486149.2 linkuse as main transcript	c.-1060G>A		5_prime_UTR_variant	2/3	1		ENSP00000457640.1		A0A0C4DGM6

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

306

AN:

151598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.0128

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00202

Gnomad OTH

AF:

0.00624

GnomAD3 exomes

AF:

0.00291

AC:

732

AN:

251310

Hom.:

AF XY:

0.00312

AC XY:

424

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00178

AC:

2581

AN:

1447616

Hom.:

Cov.:

166

AF XY:

0.00187

AC XY:

1349

AN XY:

720434

show subpopulations

Gnomad4 AFR exome

AF:

0.00160

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00302

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

151714

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

157

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000411

Gnomad4 AMR

AF:

0.00269

Gnomad4 ASJ

AF:

0.0128

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00230

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.00202

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.00270

Hom.:

EpiCase

AF:

0.00263

EpiControl

AF:

0.00291

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

Nov 01, 2024

MUC21: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.51

DANN

Benign

0.41

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