chr12-40521024-G-T

Variant names:

• chr12-40521024-G-T
• rs10878731
• ENST00000454784.10:c.20617+56G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454784.10(MUC19):​c.20617+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 978,358 control chromosomes in the GnomAD database, including 17,866 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 0.19 (2693 hom., cov: 33)
  • Exomes 𝑓: 0.19 (15173 hom.)
• Consequence: MUC19 ENST00000454784.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737
• Publications: 6 publications found

Genes affected

MUC19 (HGNC:14362): (mucin 19, oligomeric) This gene encodes a member of the gel-forming mucin protein family. Mucin family members are glycoproteins that have tandem repeats which are extensively O-glycosylated. The structural features of mucin proteins are responsible for the gel-like properties of mucus. The encoded protein may be involved in disruption of the ocular surface in Sjogren syndrome. [provided by RefSeq, Apr 2014]

ENSG00000296211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC19	NM_173600.2	c.20563+56G>T		intron_variant	Intron 99 of 171		NP_775871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.20617+56G>T		intron_variant	Intron 99 of 172	5		ENSP00000508949.1
MUC19	ENST00000398702.7	n.253+56G>T		intron_variant	Intron 2 of 6	4
ENSG00000296211	ENST00000737355.1	n.441-2007C>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28251 AN: 151986 Hom.: 2692 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.191 AC: 157418 AN: 826254 Hom.: 15173 AF XY: 0.190 AC XY: 72877 AN XY: 382926

African (AFR) AF: 0.178 AC: 2747 AN: 15456

American (AMR) AF: 0.200 AC: 224 AN: 1118

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 826 AN: 5200

East Asian (EAS) AF: 0.210 AC: 786 AN: 3746

South Asian (SAS) AF: 0.138 AC: 2328 AN: 16812

European-Finnish (FIN) AF: 0.181 AC: 1673 AN: 9224

Middle Eastern (MID) AF: 0.147 AC: 477 AN: 3240

European-Non Finnish (NFE) AF: 0.193 AC: 143618 AN: 744208

Other (OTH) AF: 0.174 AC: 4739 AN: 27250

GnomAD4 genome AF: 0.186 AC: 28263 AN: 152104 Hom.: 2693 Cov.: 33 AF XY: 0.183 AC XY: 13631 AN XY: 74360

African (AFR) AF: 0.171 AC: 7083 AN: 41496

American (AMR) AF: 0.188 AC: 2865 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5168

South Asian (SAS) AF: 0.129 AC: 623 AN: 4826

European-Finnish (FIN) AF: 0.182 AC: 1928 AN: 10578

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13445 AN: 67980

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.186 Hom.: 363

Bravo AF: 0.188

Asia WGS AF: 0.150 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.99
DANN	Benign	0.35
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10878731; hg19: chr12-40914826;