NM_001304359.2:c.140G>A

Variant names:

• chr11-1160678-G-A
• rs55846509
• NM_001304359.2:c.140G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001304359.2(MUC5AC):​c.140G>A​(p.Arg47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,609,140 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (33 hom., cov: 33)
  • Exomes 𝑓: 0.021 (391 hom.)
• Consequence: MUC5AC NM_001304359.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031018555).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0155 (2358/152290) while in subpopulation NFE AF = 0.0237 (1611/68004). AF 95% confidence interval is 0.0227. There are 33 homozygotes in GnomAd4. There are 1134 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304359.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	NM_001304359.2	MANE Select	c.140G>A	p.Arg47Gln	missense	Exon 2 of 49	NP_001291288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.140G>A	p.Arg47Gln	missense	Exon 2 of 49	ENSP00000485659.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2358 AN: 152172 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0156 AC: 3678 AN: 235612 AF XY: 0.0157

Gnomad AFR exome AF: 0.00305

Gnomad AMR exome AF: 0.00933

Gnomad ASJ exome AF: 0.00657

Gnomad EAS exome AF: 0.0000566

Gnomad FIN exome AF: 0.0311

Gnomad NFE exome AF: 0.0226

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.0208 AC: 30295 AN: 1456850 Hom.: 391 Cov.: 32 AF XY: 0.0202 AC XY: 14621 AN XY: 724706

African (AFR) AF: 0.00338 AC: 113 AN: 33440

American (AMR) AF: 0.00981 AC: 437 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00656 AC: 171 AN: 26078

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39590

South Asian (SAS) AF: 0.00584 AC: 501 AN: 85842

European-Finnish (FIN) AF: 0.0277 AC: 1391 AN: 50246

Middle Eastern (MID) AF: 0.0127 AC: 73 AN: 5766

European-Non Finnish (NFE) AF: 0.0238 AC: 26454 AN: 1111046

Other (OTH) AF: 0.0191 AC: 1153 AN: 60274

GnomAD4 genome AF: 0.0155 AC: 2358 AN: 152290 Hom.: 33 Cov.: 33 AF XY: 0.0152 AC XY: 1134 AN XY: 74474

African (AFR) AF: 0.00392 AC: 163 AN: 41564

American (AMR) AF: 0.0116 AC: 177 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4832

European-Finnish (FIN) AF: 0.0315 AC: 335 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1611 AN: 68004

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.0165 Hom.: 19

Bravo AF: 0.0140

ESP6500AA AF: 0.00400 AC: 7

ESP6500EA AF: 0.0254 AC: 101

ExAC AF: 0.0164 AC: 1906

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.46
DANN	Benign	0.66
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.96	T
PhyloP100		-2.4
Sift4G	Benign	0.42	T
Vest4		0.026
ClinPred		0.00028	T
GERP RS		-1.7
Varity_R		0.028
gMVP		0.44

Splicing

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

Other links and lift over

dbSNP: rs55846509; hg19: chr11-1154294; COSMIC: COSV99050037;