11-1201105-A-G

Variant summary

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

The NM_001304359.2(MUC5AC):c.*403A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 177,988 control chromosomes in the GnomAD database, including 2,747 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 0.16 (2235 hom., cov: 33)
  • Exomes 𝑓: 0.18 (512 hom.)
• Consequence: MUC5AC NM_001304359.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73

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 (Cadd=0.046).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5AC	NM_001304359.2	c.*403A>G		3_prime_UTR_variant	49/49	ENST00000621226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5AC	ENST00000621226.2	c.*403A>G		3_prime_UTR_variant	49/49	5	NM_001304359.2	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24601 AN: 152028 Hom.: 2235 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.181 AC: 4679 AN: 25842 Hom.: 512 Cov.: 0 AF XY: 0.182 AC XY: 2375 AN XY: 13044

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0867

Gnomad4 EAS exome AF: 0.00824

Gnomad4 SAS exome AF: 0.0676

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.162 AC: 24597 AN: 152146 Hom.: 2235 Cov.: 33 AF XY: 0.161 AC XY: 12009 AN XY: 74378

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.140

Alfa AF: 0.178 Hom.: 294

Bravo AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Cadd	Benign	0.046

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13380; hg19: -;