6-30986468-T-C

Variant names:

• chr6-30986468-T-C
• rs1634730
• NM_001010909.5:c.293T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010909.5(MUC21):​c.293T>C​(p.Val98Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 149,940 control chromosomes in the GnomAD database, including 41,921 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (41921 hom., cov: 29)
  • Exomes 𝑓: 0.71 (359432 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC21 NM_001010909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5553065E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC21	NM_001010909.5	c.293T>C	p.Val98Ala	missense_variant	Exon 2 of 3	ENST00000376296.3	NP_001010909.2
MUC21	NR_130720.3	n.676T>C		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	c.293T>C	p.Val98Ala	missense_variant	Exon 2 of 3	1	NM_001010909.5	ENSP00000365473.3
MUC21	ENST00000486149.2	c.-1070T>C		5_prime_UTR_variant	Exon 2 of 3	1		ENSP00000457640.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 111950 AN: 149824 Hom.: 41889 Cov.: 29

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.770

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.707 AC: 1010681 AN: 1430366 Hom.: 359432 Cov.: 119 AF XY: 0.704 AC XY: 501388 AN XY: 711986

African (AFR) AF: 0.835 AC: 26955 AN: 32286

American (AMR) AF: 0.656 AC: 28393 AN: 43266

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 20784 AN: 25552

East Asian (EAS) AF: 0.554 AC: 21493 AN: 38778

South Asian (SAS) AF: 0.609 AC: 51324 AN: 84258

European-Finnish (FIN) AF: 0.676 AC: 35953 AN: 53198

Middle Eastern (MID) AF: 0.721 AC: 4102 AN: 5690

European-Non Finnish (NFE) AF: 0.716 AC: 779390 AN: 1088142

Other (OTH) AF: 0.714 AC: 42287 AN: 59196

GnomAD4 genome AF: 0.747 AC: 112029 AN: 149940 Hom.: 41921 Cov.: 29 AF XY: 0.742 AC XY: 54288 AN XY: 73192

African (AFR) AF: 0.834 AC: 34165 AN: 40978

American (AMR) AF: 0.708 AC: 10689 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2823 AN: 3452

East Asian (EAS) AF: 0.619 AC: 3067 AN: 4958

South Asian (SAS) AF: 0.608 AC: 2821 AN: 4642

European-Finnish (FIN) AF: 0.701 AC: 7240 AN: 10322

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.723 AC: 48624 AN: 67220

Other (OTH) AF: 0.766 AC: 1595 AN: 2082

Alfa AF: 0.677 Hom.: 24297

Bravo AF: 0.755

TwinsUK AF: 0.715 AC: 2650

ALSPAC AF: 0.729 AC: 2811

ESP6500AA AF: 0.817 AC: 3601

ESP6500EA AF: 0.719 AC: 6186

ExAC AF: 0.697 AC: 84495

Asia WGS AF: 0.589 AC: 2044 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.017
DANN	Benign	0.17
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.000016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.1
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.0030
Sift	Benign	0.73	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.17
ClinPred		0.033	T
GERP RS		-2.0
Varity_R		0.016
gMVP		0.041
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1634730; hg19: chr6-30954245; COSMIC: COSV66220551;