chr6-30987582-G-A

Variant names:

• chr6-30987582-G-A
• rs2844677
• NM_001010909.5:c.1407G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001010909.5(MUC21):​c.1407G>A​(p.Ala469Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 1,614,082 control chromosomes in the GnomAD database, including 5,558 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.092 (786 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4772 hom.)
• Consequence: MUC21 NM_001010909.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.194 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC21	NM_001010909.5	c.1407G>A	p.Ala469Ala	synonymous_variant	Exon 2 of 3	ENST00000376296.3	NP_001010909.2
MUC21	NR_130720.3	n.1790G>A		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.1407G>A	p.Ala469Ala	synonymous_variant	Exon 2 of 3	1	NM_001010909.5	ENSP00000365473.3
MUC21	ENST00000486149.2	c.45G>A	p.Ala15Ala	synonymous_variant	Exon 2 of 3	1		ENSP00000457640.1

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14040 AN: 152150 Hom.: 784 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.0802 AC: 20152 AN: 251342 AF XY: 0.0775

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.0443

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.0313

Gnomad NFE exome AF: 0.0627

Gnomad OTH exome AF: 0.0828

GnomAD4 exome AF: 0.0750 AC: 109657 AN: 1461814 Hom.: 4772 Cov.: 39 AF XY: 0.0741 AC XY: 53879 AN XY: 727204

African (AFR) AF: 0.140 AC: 4676 AN: 33476

American (AMR) AF: 0.130 AC: 5812 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 1200 AN: 26136

East Asian (EAS) AF: 0.143 AC: 5674 AN: 39700

South Asian (SAS) AF: 0.0803 AC: 6925 AN: 86256

European-Finnish (FIN) AF: 0.0334 AC: 1784 AN: 53418

Middle Eastern (MID) AF: 0.0484 AC: 279 AN: 5768

European-Non Finnish (NFE) AF: 0.0707 AC: 78566 AN: 1111946

Other (OTH) AF: 0.0785 AC: 4741 AN: 60396

GnomAD4 genome AF: 0.0923 AC: 14057 AN: 152268 Hom.: 786 Cov.: 32 AF XY: 0.0910 AC XY: 6773 AN XY: 74452

African (AFR) AF: 0.142 AC: 5896 AN: 41530

American (AMR) AF: 0.128 AC: 1964 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5190

South Asian (SAS) AF: 0.0905 AC: 437 AN: 4828

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10626

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0652 AC: 4435 AN: 68016

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0751 Hom.: 2048

Bravo AF: 0.103

Asia WGS AF: 0.138 AC: 479 AN: 3478

EpiCase AF: 0.0643

EpiControl AF: 0.0677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.43
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2844677; hg19: chr6-30955359; COSMIC: COSV107497269;