6-31025688-C-T

Variant names:

• chr6-31025688-C-T
• rs759668593
• NM_001395414.1:c.257C>T

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.257C>T​(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,377,478 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. A86G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: MUC22 NM_001395414.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• 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=0.06116265).

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.257C>T	p.Ala86Val	missense	Exon 2 of 4	NP_001382343.1	E2RYF6
	MUC22	NM_001318484.1		c.266C>T	p.Ala89Val	missense	Exon 3 of 5	NP_001305413.1	E2RYF6
	MUC22	NM_001198815.1		c.257C>T	p.Ala86Val	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.257C>T	p.Ala86Val	missense	Exon 2 of 4	ENSP00000455906.1	E2RYF6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000779 AC: 1 AN: 128360 AF XY: 0.0000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000210

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000152 AC: 21 AN: 1377478 Hom.: 0 Cov.: 75 AF XY: 0.0000206 AC XY: 14 AN XY: 679684

African (AFR) AF: 0.00 AC: 0 AN: 31418

American (AMR) AF: 0.00 AC: 0 AN: 35414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25012

East Asian (EAS) AF: 0.00 AC: 0 AN: 35532

South Asian (SAS) AF: 0.00 AC: 0 AN: 78858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.0000195 AC: 21 AN: 1074310

Other (OTH) AF: 0.00 AC: 0 AN: 57594

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.093
DANN	Benign	0.77
DEOGEN2	Benign	0.0028	T
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.061	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.8
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.16	N
Sift	Benign	1.0	T
Sift4G	Benign	0.25	T
Vest4		0.090
MVP		0.12
GERP RS		1.1
Varity_R		0.026
gMVP		0.0071
Mutation Taster		=96/4	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: rs759668593; hg19: chr6-30993465;