NM_001010909.5:c.375C>T

Variant names:

• chr6-30986550-C-T
• rs149194643
• NM_001010909.5:c.375C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001010909.5(MUC21):​c.375C>T​(p.Ser125Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 127,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC21 NM_001010909.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-30986550-C-T is Benign according to our data. Variant chr6-30986550-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.47 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010909.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC21	NM_001010909.5	MANE Select	c.375C>T	p.Ser125Ser	synonymous	Exon 2 of 3	NP_001010909.2	Q5SSG8-1
	MUC21	NR_130720.3		n.758C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC21	ENST00000376296.3	TSL:1 MANE Select	c.375C>T	p.Ser125Ser	synonymous	Exon 2 of 3	ENSP00000365473.3	Q5SSG8-1
	MUC21	ENST00000486149.2	TSL:1	c.-988C>T		5_prime_UTR	Exon 2 of 3	ENSP00000457640.1	A0A0C4DGM6

Frequencies

GnomAD3 genomes AF: 0.0000313 AC: 4 AN: 127650 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000814

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000363 AC: 7 AN: 193050 AF XY: 0.0000574

Gnomad AFR exome AF: 0.0000830

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.000167

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000111

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000753 AC: 88 AN: 1168288 Hom.: 0 Cov.: 164 AF XY: 0.0000860 AC XY: 50 AN XY: 581546

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000195 AC: 5 AN: 25668

American (AMR) AF: 0.000569 AC: 19 AN: 33388

Ashkenazi Jewish (ASJ) AF: 0.000175 AC: 3 AN: 17166

East Asian (EAS) AF: 0.000127 AC: 4 AN: 31598

South Asian (SAS) AF: 0.000112 AC: 8 AN: 71498

European-Finnish (FIN) AF: 0.0000219 AC: 1 AN: 45756

Middle Eastern (MID) AF: 0.000210 AC: 1 AN: 4762

European-Non Finnish (NFE) AF: 0.0000528 AC: 47 AN: 890258

Other (OTH) AF: 0.00 AC: 0 AN: 48194

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000313 AC: 4 AN: 127650 Hom.: 0 Cov.: 32 AF XY: 0.0000321 AC XY: 2 AN XY: 62380

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000873 AC: 3 AN: 34376

American (AMR) AF: 0.0000814 AC: 1 AN: 12278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2468

East Asian (EAS) AF: 0.00 AC: 0 AN: 4516

South Asian (SAS) AF: 0.00 AC: 0 AN: 4208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57520

Other (OTH) AF: 0.00 AC: 0 AN: 1740

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0161 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs149194643; hg19: chr6-30954327; COSMIC: COSV66220266;