chr6-31025783-A-G

Position:

• chr6-31025783-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395414.1(MUC22):​c.352A>G​(p.Thr118Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15

Genes affected

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

ACMG classification

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=0.10045785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.352A>G	p.Thr118Ala	missense_variant	2/4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.361A>G	p.Thr121Ala	missense_variant	3/5		NP_001305413.1
MUC22	NM_001198815.1	c.352A>G	p.Thr118Ala	missense_variant	3/5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.352A>G	p.Thr118Ala	missense_variant	2/4	2	NM_001395414.1	ENSP00000455906	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.352A>G (p.T118A) 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 352, causing the threonine (T) at amino acid position 118 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	0.090
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.64
DANN	Benign	0.36
DEOGEN2	Benign	0.0023	T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.10	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-0.59	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.92	T
Vest4		0.088
MVP		0.22
GERP RS		2.3
Varity_R		0.073
gMVP		0.012

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30993560;