Variant 6-30986661-C-T 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.486C>T(p.Ala162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00881 in 1,469,252 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 18 hom., cov: 29)

Exomes 𝑓: 0.0089 ( 128 hom. )

Consequence

MUC21
NM_001010909.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.85

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:

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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=-0.83).

BP6

Variant 6-30986661-C-T is Benign according to our data. Variant chr6-30986661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656351.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00893 (11997/1343526) while in subpopulation EAS AF= 0.0351 (1195/34032). AF 95% confidence interval is 0.0335. There are 128 homozygotes in gnomad4_exome. There are 6150 alleles in male gnomad4_exome subpopulation. Median coverage is 163. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC21	NM_001010909.5 linkuse as main transcript	c.486C>T	p.Ala162=	synonymous_variant	2/3	ENST00000376296.3
MUC21	NR_130720.3 linkuse as main transcript	n.869C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC21	ENST00000376296.3 linkuse as main transcript	c.486C>T	p.Ala162=	synonymous_variant	2/3	1	NM_001010909.5	P1	Q5SSG8-1
MUC21	ENST00000486149.2 linkuse as main transcript	c.-877C>T		5_prime_UTR_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.00760

AC:

955

AN:

125638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00592

Gnomad AMI

AF:

0.00242

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0278

Gnomad EAS

AF:

0.00422

Gnomad SAS

AF:

0.00459

Gnomad FIN

AF:

0.00345

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00848

GnomAD3 exomes

AF:

0.00337

AC:

784

AN:

232332

Hom.:

AF XY:

0.00307

AC XY:

388

AN XY:

126360

show subpopulations

Gnomad AFR exome

AF:

0.00629

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00455

Gnomad EAS exome

AF:

0.00394

Gnomad SAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.00282

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00451

GnomAD4 exome

AF:

0.00893

AC:

11997

AN:

1343526

Hom.:

128

Cov.:

163

AF XY:

0.00921

AC XY:

6150

AN XY:

667576

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.00341

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00706

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.00757

AC:

952

AN:

125726

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

492

AN XY:

61516

show subpopulations

Gnomad4 AFR

AF:

0.00584

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0278

Gnomad4 EAS

AF:

0.00422

Gnomad4 SAS

AF:

0.00459

Gnomad4 FIN

AF:

0.00345

Gnomad4 NFE

AF:

0.00815

Gnomad4 OTH

AF:

0.00958

Alfa

AF:

0.00986

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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

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