rs772843697

Variant names:

• chr6-30986839-GC-G
• rs772843697
• NM_001010909.5:c.665delC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001010909.5(MUC21):​c.665delC​(p.Ala222ValfsTer221) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 144,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC21 NM_001010909.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-30986839-GC-G is Benign according to our data. Variant chr6-30986839-GC-G is described in ClinVar as [Benign]. Clinvar id is 243064.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC21	NM_001010909.5	c.665delC	p.Ala222ValfsTer221	frameshift_variant	Exon 2 of 3	ENST00000376296.3	NP_001010909.2
MUC21	NR_130720.3	n.1048delC		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.665delC	p.Ala222ValfsTer221	frameshift_variant	Exon 2 of 3	1	NM_001010909.5	ENSP00000365473.3
MUC21	ENST00000486149.2	c.-698delC		5_prime_UTR_variant	Exon 2 of 3	1		ENSP00000457640.1

Frequencies

GnomAD3 genomes AF: 0.0000621 AC: 9 AN: 144824 Hom.: 0 Cov.: 29

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: 0.000121

Gnomad OTH AF: 0.000508

GnomAD2 exomes AF: 0.000136 AC: 34 AN: 250912 AF XY: 0.000147

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000138 AC: 199 AN: 1437852 Hom.: 0 Cov.: 180 AF XY: 0.000138 AC XY: 99 AN XY: 715034

African (AFR) AF: 0.0000307 AC: 1 AN: 32574

American (AMR) AF: 0.00 AC: 0 AN: 42840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25216

East Asian (EAS) AF: 0.00 AC: 0 AN: 37692

South Asian (SAS) AF: 0.00 AC: 0 AN: 84508

European-Finnish (FIN) AF: 0.0000958 AC: 5 AN: 52174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.000169 AC: 186 AN: 1098332

Other (OTH) AF: 0.000119 AC: 7 AN: 58858

GnomAD4 genome AF: 0.0000621 AC: 9 AN: 144824 Hom.: 0 Cov.: 29 AF XY: 0.0000426 AC XY: 3 AN XY: 70476

African (AFR) AF: 0.00 AC: 0 AN: 38698

American (AMR) AF: 0.00 AC: 0 AN: 14548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4688

South Asian (SAS) AF: 0.00 AC: 0 AN: 4516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.000121 AC: 8 AN: 66318

Other (OTH) AF: 0.000508 AC: 1 AN: 1970

Alfa AF: 0.000169 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 01, 2015

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Benign. This variant was found to be outside the region (chr6:32557483-35479574) linked to juvenile cataracts using SNP-based fine mapping. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=181/19	disease causing (fs/PTC)

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: rs772843697; hg19: chr6-30954616;