6-31025715-C-T

Variant names:

• chr6-31025715-C-T
• rs747791085
• NM_001395414.1:c.284C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395414.1(MUC22):​c.284C>T​(p.Thr95Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,530,564 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T95K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06887722).

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.284C>T	p.Thr95Met	missense	Exon 2 of 4	NP_001382343.1	E2RYF6
	MUC22	NM_001318484.1		c.293C>T	p.Thr98Met	missense	Exon 3 of 5	NP_001305413.1	E2RYF6
	MUC22	NM_001198815.1		c.284C>T	p.Thr95Met	missense	Exon 3 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.284C>T	p.Thr95Met	missense	Exon 2 of 4	ENSP00000455906.1	E2RYF6

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151992 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000234 AC: 3 AN: 128274 AF XY: 0.0000428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000420

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000450 AC: 62 AN: 1378572 Hom.: 0 Cov.: 75 AF XY: 0.0000353 AC XY: 24 AN XY: 680256

African (AFR) AF: 0.0000318 AC: 1 AN: 31484

American (AMR) AF: 0.00 AC: 0 AN: 35480

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25080

East Asian (EAS) AF: 0.0000562 AC: 2 AN: 35602

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.0000512 AC: 55 AN: 1074944

Other (OTH) AF: 0.0000347 AC: 2 AN: 57670

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151992 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000567 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.98
DANN	Benign	0.60
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.069	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.59
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.32	N
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Vest4		0.16
MVP		0.41
GERP RS		0.18
Varity_R		0.037
gMVP		0.011
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs747791085; hg19: chr6-30993492;