rs937199021

Variant names:

• chr6-31026180-C-A
• NM_001395414.1:c.749C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31026180-C-A
• chr6-31026180-C-T

Variant summary

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

The NM_001395414.1(MUC22):​c.749C>A​(p.Ala250Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,371,792 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. A250V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=0.0932211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.749C>A	p.Ala250Glu	missense_variant	Exon 2 of 4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.758C>A	p.Ala253Glu	missense_variant	Exon 3 of 5		NP_001305413.1
MUC22	NM_001198815.1	c.749C>A	p.Ala250Glu	missense_variant	Exon 3 of 5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.749C>A	p.Ala250Glu	missense_variant	Exon 2 of 4	2	NM_001395414.1	ENSP00000455906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1371792 Hom.: 0 Cov.: 88 AF XY: 0.00000148 AC XY: 1 AN XY: 677066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.43
DANN	Benign	0.31
DEOGEN2	Benign	0.0031	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.093	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.28	N
Sift	Benign	0.38	T
Sift4G	Benign	0.063	T
Vest4		0.11
MVP		0.21
GERP RS		0.081
Varity_R		0.049
gMVP		0.034

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: chr6-30993957;