11-1183604-G-A

Variant summary

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

The NM_001304359.2(MUC5AC):c.5459G>A(p.Arg1820Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 629,976 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (0 hom., cov: 28)
  • Exomes 𝑓: 0.13 (7 hom.)
• Consequence: MUC5AC NM_001304359.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.361

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=0.0016388893).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5AC	NM_001304359.2	c.5459G>A	p.Arg1820Gln	missense_variant	31/49	ENST00000621226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5AC	ENST00000621226.2	c.5459G>A	p.Arg1820Gln	missense_variant	31/49	5	NM_001304359.2	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 19786 AN: 147360 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0627

Gnomad EAS AF: 0.00389

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.134 AC: 64423 AN: 482510 Hom.: 7 Cov.: 0 AF XY: 0.130 AC XY: 33429 AN XY: 256914

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0823

Gnomad4 ASJ exome AF: 0.0656

Gnomad4 EAS exome AF: 0.00362

Gnomad4 SAS exome AF: 0.0564

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.134 AC: 19782 AN: 147466 Hom.: 0 Cov.: 28 AF XY: 0.134 AC XY: 9616 AN XY: 71944

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0627

Gnomad4 EAS AF: 0.00390

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.119

Alfa AF: 0.145 Hom.: 0

ESP6500AA AF: 0.0811 AC: 142

ESP6500EA AF: 0.132 AC: 526

ExAC AF: 0.126 AC: 14988

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	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	15
DEOGEN2	Benign	0.082	T
FATHMM_MKL	Benign	0.050	N
MetaRNN	Benign	0.0016	T
Sift4G	Benign	0.092	T
Vest4		0.11
GERP RS		0.74
Varity_R		0.044
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: rs878949904; hg19: chr11-1213481;