Variant chr6-31026260-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.84

Variant links:

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUC22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060694754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MUC22	NM_001395414.1 linkuse as main transcript	c.829A>G	p.Thr277Ala	missense_variant	2/4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1 linkuse as main transcript	c.838A>G	p.Thr280Ala	missense_variant	3/5		NP_001305413.1
MUC22	NM_001198815.1 linkuse as main transcript	c.829A>G	p.Thr277Ala	missense_variant	3/5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1 linkuse as main transcript	c.829A>G	p.Thr277Ala	missense_variant	2/4	2	NM_001395414.1	ENSP00000455906	P1

Frequencies

GnomAD3 genomes

AF:

0.0000225

AC:

AN:

133084

Hom.:

Cov.:

show subpopulations

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000149

AC:

AN:

1205372

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

594776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000170

Gnomad4 OTH exome

AF:

0.0000393

GnomAD4 genome

AF:

0.0000225

AC:

AN:

133194

Hom.:

Cov.:

AF XY:

0.0000309

AC XY:

AN XY:

64794

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000125

Gnomad4 NFE

AF:

0.0000172

Gnomad4 OTH

AF:

0.000553

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.829A>G (p.T277A) alteration is located in exon 3 (coding exon 2) of the MUC22 gene. This alteration results from a A to G substitution at nucleotide position 829, causing the threonine (T) at amino acid position 277 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.0

DANN

Benign

0.38

DEOGEN2

Benign

0.0037

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.39

M_CAP

Benign

0.0066

MetaRNN

Benign

0.061

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.1

Sift

Benign

0.15

Sift4G

Benign

0.091

Vest4

0.056

MVP

0.12

GERP RS

-4.0

Varity_R

0.036

gMVP

0.015

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over