Variant 6-31026326-A-C 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.895A>C(p.Thr299Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,504,824 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T299I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MUC22
NM_001395414.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.340

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=0.051599056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MUC22	NM_001395414.1 linkuse as main transcript	c.895A>C	p.Thr299Pro	missense_variant	2/4	ENST00000561890.1
MUC22	NM_001318484.1 linkuse as main transcript	c.904A>C	p.Thr302Pro	missense_variant	3/5
MUC22	NM_001198815.1 linkuse as main transcript	c.895A>C	p.Thr299Pro	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC22	ENST00000561890.1 linkuse as main transcript	c.895A>C	p.Thr299Pro	missense_variant	2/4	2	NM_001395414.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000700

AC:

AN:

142764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000601

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

125826

Hom.:

AF XY:

0.0000726

AC XY:

AN XY:

68886

show subpopulations

Gnomad AFR exome

AF:

0.000823

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000481

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1362060

Hom.:

Cov.:

AF XY:

0.0000119

AC XY:

AN XY:

671890

show subpopulations

Gnomad4 AFR exome

AF:

0.000286

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000169

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.40e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000700

AC:

AN:

142764

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

69148

show subpopulations

Gnomad4 AFR

AF:

0.000179

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000601

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 17, 2023

The c.895A>C (p.T299P) alteration is located in exon 3 (coding exon 2) of the MUC22 gene. This alteration results from a A to C substitution at nucleotide position 895, causing the threonine (T) at amino acid position 299 to be replaced by a proline (P). 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

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.0

DANN

Benign

0.25

DEOGEN2

Benign

0.0041

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.49

M_CAP

Benign

0.074

MetaRNN

Benign

0.052

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.17

PROVEAN

Benign

-1.1

Sift

Benign

0.19

Sift4G

Uncertain

0.010

Vest4

0.20

MVP

0.23

GERP RS

1.4

Varity_R

0.13

gMVP

0.022

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