11-1188446-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.10301C>T(p.Pro3434Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 669,808 control chromosomes in the GnomAD database, including 10,010 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 0.16 (2267 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7743 hom.)
• Consequence: MUC5AC NM_001304359.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.00400

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=0.002968818).
• 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.10301C>T	p.Pro3434Leu	missense_variant	31/49	ENST00000621226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5AC	ENST00000621226.2	c.10301C>T	p.Pro3434Leu	missense_variant	31/49	5	NM_001304359.2	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24646 AN: 151516 Hom.: 2263 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.156 AC: 80639 AN: 518174 Hom.: 7743 Cov.: 0 AF XY: 0.150 AC XY: 41821 AN XY: 277974

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.0748

Gnomad4 EAS exome AF: 0.00370

Gnomad4 SAS exome AF: 0.0641

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.163 AC: 24659 AN: 151634 Hom.: 2267 Cov.: 32 AF XY: 0.162 AC XY: 12024 AN XY: 74084

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.140

Alfa AF: 0.171 Hom.: 170

Bravo AF: 0.153

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	0.25
Cadd	Benign	7.3
DEOGEN2	Benign	0.091	T
MetaRNN	Benign	0.0030	T
Sift4G	Uncertain	0.0070	D
Vest4		0.074
gMVP		0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1269243287; hg19: -;