chr6-31026260-A-G

Variant names:

• chr6-31026260-A-G
• rs1308190245
• NM_001395414.1:c.829A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395414.1(MUC22):​c.829A>G​(p.Thr277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 133,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000015 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.84
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060694754).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC22	NM_001395414.1	MANE Select	c.829A>G	p.Thr277Ala	missense	Exon 2 of 4	NP_001382343.1	E2RYF6
	MUC22	NM_001318484.1		c.838A>G	p.Thr280Ala	missense	Exon 3 of 5	NP_001305413.1	E2RYF6
	MUC22	NM_001198815.1		c.829A>G	p.Thr277Ala	missense	Exon 3 of 5	NP_001185744.1	E2RYF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC22	ENST00000561890.1	TSL:2 MANE Select	c.829A>G	p.Thr277Ala	missense	Exon 2 of 4	ENSP00000455906.1	E2RYF6

Frequencies

GnomAD3 genomes AF: 0.0000225 AC: 3 AN: 133084 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000172

Gnomad OTH AF: 0.000559

GnomAD2 exomes AF: 0.00 AC: 0 AN: 117900 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000149 AC: 18 AN: 1205372 Hom.: 2 Cov.: 68 AF XY: 0.0000202 AC XY: 12 AN XY: 594776

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29918

American (AMR) AF: 0.00 AC: 0 AN: 30502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22202

East Asian (EAS) AF: 0.00 AC: 0 AN: 33672

South Asian (SAS) AF: 0.00 AC: 0 AN: 68438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4628

European-Non Finnish (NFE) AF: 0.0000170 AC: 16 AN: 939372

Other (OTH) AF: 0.0000393 AC: 2 AN: 50902

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000444089), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000225 AC: 3 AN: 133194 Hom.: 0 Cov.: 30 AF XY: 0.0000309 AC XY: 2 AN XY: 64794

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39100

American (AMR) AF: 0.00 AC: 0 AN: 12924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3000

East Asian (EAS) AF: 0.00 AC: 0 AN: 4884

South Asian (SAS) AF: 0.00 AC: 0 AN: 4282

European-Finnish (FIN) AF: 0.000125 AC: 1 AN: 8012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.0000172 AC: 1 AN: 58168

Other (OTH) AF: 0.000553 AC: 1 AN: 1808

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000000565104), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.38
DEOGEN2	Benign	0.0037	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.061	T
MutationAssessor	Benign	0.69	N
PhyloP100		-3.8
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.1	N
Sift	Benign	0.15	T
Sift4G	Benign	0.091	T
Vest4		0.056
MVP		0.12
GERP RS		-4.0
Varity_R		0.036
gMVP		0.015
Mutation Taster		=100/0	polymorphism

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: rs1308190245; hg19: chr6-30994037;