Variant 6-31026269-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395414.1(MUC22):c.838A>T(p.Ile280Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 113,924 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 0.00030 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000086 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

MUC22
NM_001395414.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.04

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02104342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MUC22	NM_001395414.1 linkuse as main transcript	c.838A>T	p.Ile280Phe	missense_variant	2/4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1 linkuse as main transcript	c.847A>T	p.Ile283Phe	missense_variant	3/5		NP_001305413.1
MUC22	NM_001198815.1 linkuse as main transcript	c.838A>T	p.Ile280Phe	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.838A>T	p.Ile280Phe	missense_variant	2/4	2	NM_001395414.1	ENSP00000455906	P1

Frequencies

GnomAD3 genomes

AF:

0.000299

AC:

AN:

113818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00144

Gnomad SAS

AF:

0.00112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000219

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000858

AC:

AN:

1154410

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

569078

show subpopulations

Gnomad4 AFR exome

AF:

0.000171

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.0000474

Gnomad4 EAS exome

AF:

0.000273

Gnomad4 SAS exome

AF:

0.000261

Gnomad4 FIN exome

AF:

0.0000430

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.000123

GnomAD4 genome

AF:

0.000298

AC:

AN:

113924

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

55252

show subpopulations

Gnomad4 AFR

AF:

0.000349

Gnomad4 AMR

AF:

0.0000925

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00145

Gnomad4 SAS

AF:

0.00112

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000219

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00138

AC:

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

Aug 16, 2022

The c.838A>T (p.I280F) alteration is located in exon 3 (coding exon 2) of the MUC22 gene. This alteration results from a A to T substitution at nucleotide position 838, causing the isoleucine (I) at amino acid position 280 to be replaced by a phenylalanine (F). 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

0.20

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.9

DANN

Benign

0.30

DEOGEN2

Benign

0.0060

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.55

M_CAP

Benign

0.012

MetaRNN

Benign

0.021

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.83

Sift

Benign

0.083

Sift4G

Uncertain

0.044

Vest4

0.045

MVP

0.17

GERP RS

0.50

Varity_R

0.073

gMVP

0.023

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