chr6-31025928-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395414.1(MUC22):​c.497C>T​(p.Thr166Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000782 in 1,535,094 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

MUC22
NM_001395414.1 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.710
Variant links:
Genes affected
MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07838833).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUC22NM_001395414.1 linkuse as main transcriptc.497C>T p.Thr166Met missense_variant 2/4 ENST00000561890.1 NP_001382343.1
MUC22NM_001318484.1 linkuse as main transcriptc.506C>T p.Thr169Met missense_variant 3/5 NP_001305413.1
MUC22NM_001198815.1 linkuse as main transcriptc.497C>T p.Thr166Met missense_variant 3/5 NP_001185744.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUC22ENST00000561890.1 linkuse as main transcriptc.497C>T p.Thr166Met missense_variant 2/42 NM_001395414.1 ENSP00000455906 P1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151734
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000485
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000233
AC:
3
AN:
128638
Hom.:
0
AF XY:
0.0000284
AC XY:
2
AN XY:
70352
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000411
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000956
Gnomad SAS exome
AF:
0.0000447
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000651
AC:
9
AN:
1383360
Hom.:
0
Cov.:
86
AF XY:
0.0000103
AC XY:
7
AN XY:
682532
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151734
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74088
show subpopulations
Gnomad4 AFR
AF:
0.0000485
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

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 submitterclinical testingAmbry GeneticsApr 24, 2024The c.497C>T (p.T166M) alteration is located in exon 3 (coding exon 2) of the MUC22 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the threonine (T) at amino acid position 166 to be replaced by a methionine (M). 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
0.13
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
15
DANN
Benign
0.22
DEOGEN2
Benign
0.0028
T
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.078
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.17
T
PROVEAN
Benign
-0.59
N
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0080
D
Vest4
0.091
MVP
0.19
GERP RS
-2.2
Varity_R
0.040
gMVP
0.013

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.

Other links and lift over

dbSNP: rs920021361; hg19: chr6-30993705; API