chr6-31034839-C-A

Variant names:

• chr6-31034839-C-A
• NM_001395414.1:c.5223C>A
• MUC22 p.His1741Gln

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395414.1(MUC22):​c.5223C>A​(p.His1741Gln) 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. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06431565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC22	NM_001395414.1	MANE Select	c.5223C>A	p.His1741Gln	missense	Exon 4 of 4	NP_001382343.1	E2RYF6
	MUC22	NM_001318484.1		c.5232C>A	p.His1744Gln	missense	Exon 5 of 5	NP_001305413.1	E2RYF6
	MUC22	NM_001198815.1		c.5223C>A	p.His1741Gln	missense	Exon 5 of 5	NP_001185744.1	E2RYF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC22	ENST00000561890.1	TSL:2 MANE Select	c.5223C>A	p.His1741Gln	missense	Exon 4 of 4	ENSP00000455906.1	E2RYF6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.39
DANN	Benign	0.54
DEOGEN2	Benign	0.0043	T
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.064	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.90	N
Sift	Benign	0.48	T
Sift4G	Benign	0.41	T
Varity_R		0.035
gMVP		0.47
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-31002616;