NM_001414686.1:c.4344A>G

Variant names:

• chr19-8977341-T-C
• rs1596797
• NM_001401501.2:c.3918A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-8977341-T-C
• chrNW_025791807.1-227109-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001414686.1(MUC16):​c.4344A>G​(p.Lys1448Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC16 NM_001414686.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 28 publications found

Genes affected

MUC16 (HGNC:15582): (mucin 16, cell surface associated) This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414686.1. 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
	MUC16	NM_001401501.2	MANE Select	c.3918A>G	p.Lys1306Lys	synonymous	Exon 4 of 93	NP_001388430.1	A0AAG2UXK0
	MUC16	NM_001414686.1		c.4344A>G	p.Lys1448Lys	synonymous	Exon 5 of 94	NP_001401615.1
	MUC16	NM_001414687.1		c.3798A>G	p.Lys1266Lys	synonymous	Exon 1 of 90	NP_001401616.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC16	ENST00000397910.8	TSL:5	c.3798A>G	p.Lys1266Lys	synonymous	Exon 1 of 84	ENSP00000381008.2	Q8WXI7
	MUC16	ENST00000711672.1		c.3918A>G	p.Lys1306Lys	synonymous	Exon 4 of 88	ENSP00000518832.1	A0AAA9YHI4
	MUC16	ENST00000710609.1		c.3918A>G	p.Lys1306Lys	synonymous	Exon 4 of 87	ENSP00000518375.1	A0AA34QW05

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249274 AF XY: 0.00000740

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461704 Hom.: 0 Cov.: 68 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 188946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-1.3

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: rs1596797; hg19: chr19-9088017;