6-31028355-C-T

Variant names:

• chr6-31028355-C-T
• rs12665700
• NM_001395414.1:c.2924C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [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=0.0017933547).
• 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 rank	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.2924C>T	p.Thr975Ile	missense_variant	Exon 2 of 4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.2933C>T	p.Thr978Ile	missense_variant	Exon 3 of 5		NP_001305413.1
MUC22	NM_001198815.1	c.2924C>T	p.Thr975Ile	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.2924C>T	p.Thr975Ile	missense_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.131 AC: 16790 AN: 128336 AF XY: 0.131

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 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

African (AFR) AF: 0.0575 AC: 1816 AN: 31578

American (AMR) AF: 0.171 AC: 6085 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3178 AN: 25174

East Asian (EAS) AF: 0.0612 AC: 2176 AN: 35566

South Asian (SAS) AF: 0.128 AC: 10130 AN: 79206

European-Finnish (FIN) AF: 0.213 AC: 7132 AN: 33460

Middle Eastern (MID) AF: 0.160 AC: 911 AN: 5692

European-Non Finnish (NFE) AF: 0.118 AC: 127161 AN: 1078628

Other (OTH) AF: 0.116 AC: 6708 AN: 57892

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

African (AFR) AF: 0.0594 AC: 2449 AN: 41256

American (AMR) AF: 0.143 AC: 2183 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3464

East Asian (EAS) AF: 0.0527 AC: 270 AN: 5128

South Asian (SAS) AF: 0.110 AC: 527 AN: 4806

European-Finnish (FIN) AF: 0.228 AC: 2399 AN: 10524

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8630 AN: 67838

Other (OTH) AF: 0.133 AC: 279 AN: 2098

Alfa AF: 0.123 Hom.: 3190

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
PhyloP100		0.0070
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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