6-31034839-C-T

Variant names:

• chr6-31034839-C-T
• rs4248154
• NM_001395414.1:c.5223C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001395414.1(MUC22):​c.5223C>T​(p.His1741His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,535,300 control chromosomes in the GnomAD database, including 27,879 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2470 hom., cov: 31)
  • Exomes 𝑓: 0.18 (25409 hom.)
• Consequence: MUC22 NM_001395414.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 46 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.5223C>T	p.His1741His	synonymous_variant	Exon 4 of 4	ENST00000561890.1	NP_001382343.1
MUC22	NM_001318484.1	c.5232C>T	p.His1744His	synonymous_variant	Exon 5 of 5		NP_001305413.1
MUC22	NM_001198815.1	c.5223C>T	p.His1741His	synonymous_variant	Exon 5 of 5		NP_001185744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.5223C>T	p.His1741His	synonymous_variant	Exon 4 of 4	2	NM_001395414.1	ENSP00000455906.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26139 AN: 151816 Hom.: 2461 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.200 AC: 25667 AN: 128446 AF XY: 0.205

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.270

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.184 AC: 254769 AN: 1383364 Hom.: 25409 Cov.: 36 AF XY: 0.188 AC XY: 128160 AN XY: 682582

African (AFR) AF: 0.118 AC: 3734 AN: 31594

American (AMR) AF: 0.184 AC: 6565 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3769 AN: 25180

East Asian (EAS) AF: 0.384 AC: 13712 AN: 35734

South Asian (SAS) AF: 0.271 AC: 21496 AN: 79234

European-Finnish (FIN) AF: 0.200 AC: 6705 AN: 33472

Middle Eastern (MID) AF: 0.202 AC: 1152 AN: 5696

European-Non Finnish (NFE) AF: 0.174 AC: 187750 AN: 1078848

Other (OTH) AF: 0.171 AC: 9886 AN: 57906

GnomAD4 genome AF: 0.172 AC: 26157 AN: 151936 Hom.: 2470 Cov.: 31 AF XY: 0.176 AC XY: 13066 AN XY: 74280

African (AFR) AF: 0.121 AC: 4999 AN: 41418

American (AMR) AF: 0.185 AC: 2828 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1549 AN: 5148

South Asian (SAS) AF: 0.286 AC: 1370 AN: 4794

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10566

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12489 AN: 67952

Other (OTH) AF: 0.154 AC: 324 AN: 2106

Alfa AF: 0.185 Hom.: 11560

Bravo AF: 0.165

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.34
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs4248154; hg19: chr6-31002616;