rs12179536

Variant names:

• chr6-31025813-A-G
• rs12179536
• NM_001395414.1:c.382A>G

Variant summary

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

The NM_001395414.1(MUC22):​c.382A>G​(p.Ile128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,534,794 control chromosomes in the GnomAD database, including 27,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I128M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.16 (2397 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25494 hom.)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [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=1.0362754E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.382A>G	p.Ile128Val	missense_variant	Exon 2 of 4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.391A>G	p.Ile131Val	missense_variant	Exon 3 of 5		NP_001305413.1
MUC22	NM_001198815.1	c.382A>G	p.Ile128Val	missense_variant	Exon 3 of 5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.382A>G	p.Ile128Val	missense_variant	Exon 2 of 4	2	NM_001395414.1	ENSP00000455906.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25052 AN: 151954 Hom.: 2393 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.223 AC: 28617 AN: 128570 Hom.: 3677 AF XY: 0.228 AC XY: 16065 AN XY: 70328

Gnomad AFR exome AF: 0.0816

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.182 AC: 252111 AN: 1382720 Hom.: 25494 Cov.: 83 AF XY: 0.188 AC XY: 128369 AN XY: 682262

Gnomad4 AFR exome AF: 0.0819

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.165 AC: 25061 AN: 152074 Hom.: 2397 Cov.: 32 AF XY: 0.168 AC XY: 12503 AN XY: 74352

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.166

Alfa AF: 0.183 Hom.: 4903

Bravo AF: 0.165

TwinsUK AF: 0.172 AC: 636

ALSPAC AF: 0.161 AC: 620

ExAC AF: 0.200 AC: 3588

Asia WGS AF: 0.258 AC: 893 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.57
DEOGEN2	Benign	0.0056	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.00010	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.15	T
PROVEAN	Benign	-0.12	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Vest4		0.010
GERP RS		-3.0
Varity_R		0.090
gMVP		0.0031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12179536; hg19: chr6-30993590; COSMIC: COSV73736400;