rs12665700

Positions:

• chr6-31028355-C-T

Variant summary

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

The NM_001395414.1(MUC22):​c.2924C>T​(p.Thr975Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,534,434 control chromosomes in the GnomAD database, including 13,102 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.

• Frequency:
  • Genomes: 𝑓 0.11 (1237 hom., cov: 31)
  • Exomes 𝑓: 0.12 (11865 hom.)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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=0.0017933547).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.2924C>T	p.Thr975Ile	missense_variant	2/4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.2933C>T	p.Thr978Ile	missense_variant	3/5		NP_001305413.1
MUC22	NM_001198815.1	c.2924C>T	p.Thr975Ile	missense_variant	3/5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.2924C>T	p.Thr975Ile	missense_variant	2/4	2	NM_001395414.1	ENSP00000455906.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17341 AN: 151436 Hom.: 1241 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.131 AC: 16790 AN: 128336 Hom.: 1331 AF XY: 0.131 AC XY: 9172 AN XY: 70278

Gnomad AFR exome AF: 0.0620

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0674

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.127

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.120 AC: 165297 AN: 1382876 Hom.: 11865 Cov.: 76 AF XY: 0.120 AC XY: 81901 AN XY: 682318

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0612

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.114 AC: 17343 AN: 151558 Hom.: 1237 Cov.: 31 AF XY: 0.118 AC XY: 8763 AN XY: 74080

Gnomad4 AFR AF: 0.0594

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.133

Alfa AF: 0.129 Hom.: 2309

Bravo AF: 0.109

TwinsUK AF: 0.108 AC: 401

ALSPAC AF: 0.111 AC: 426

ExAC AF: 0.0989 AC: 1405

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.49
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0018	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.0	N
Sift	Benign	0.040	D
Sift4G	Uncertain	0.0080	D
Vest4		0.011
GERP RS		2.6
Varity_R		0.089
gMVP		0.068

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: rs12665700; hg19: chr6-30996132; COSMIC: COSV105379938;