11-1180138-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304359.2(MUC5AC):c.3601C>T(p.Arg1201Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 395,884 control chromosomes in the GnomAD database, including 5,408 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1875 hom., cov: 34)
  • Exomes 𝑓: 0.16 (3533 hom.)
• Consequence: MUC5AC NM_001304359.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.228

Genes affected

MUC5AC (HGNC:7515): (mucin 5AC, oligomeric mucus/gel-forming) Predicted to be an extracellular matrix structural constituent. Involved in phosphatidylinositol-mediated signaling. Located in cytoplasm; extracellular space; and mucus layer. Implicated in dry eye syndrome. Biomarker of several diseases, including Sjogren's syndrome; biliary tract disease (multiple); cystic fibrosis; eye disease (multiple); and pancreatic cancer (multiple). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009532452).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5AC	NM_001304359.2	c.3601C>T	p.Arg1201Trp	missense_variant	27/49	ENST00000621226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5AC	ENST00000621226.2	c.3601C>T	p.Arg1201Trp	missense_variant	27/49	5	NM_001304359.2	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 21888 AN: 149392 Hom.: 1872 Cov.: 34

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.157 AC: 38655 AN: 246378 Hom.: 3533 Cov.: 0 AF XY: 0.158 AC XY: 19725 AN XY: 124916

Gnomad4 AFR exome AF: 0.0886

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.0703

Gnomad4 EAS exome AF: 0.00586

Gnomad4 SAS exome AF: 0.0609

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.147 AC: 21903 AN: 149506 Hom.: 1875 Cov.: 34 AF XY: 0.147 AC XY: 10734 AN XY: 72872

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.00407

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.130

Alfa AF: 0.158 Hom.: 188

Bravo AF: 0.132

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Keratoconus Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Apr 01, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
Cadd	Benign	16
DEOGEN2	Uncertain	0.50	D
MetaRNN	Benign	0.0095	T
Sift4G	Uncertain	0.022	D
Vest4		0.27
gMVP		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878913005; hg19: -;