12-40400191-C-T

Variant names:

• chr12-40400191-C-T
• rs1820544
• ENST00000454784.10:c.112+124C>T

Variant summary

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

The ENST00000454784.10(MUC19):​c.112+124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 464,796 control chromosomes in the GnomAD database, including 34,180 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 0.39 (11788 hom., cov: 32)
  • Exomes 𝑓: 0.37 (22392 hom.)
• Consequence: MUC19 ENST00000454784.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• 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]

ENSG00000258167 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC19	NM_173600.2	c.112+124C>T		intron_variant	Intron 3 of 171		NP_775871.2
LOC105369736	XR_007063562.1	n.305-4205G>A		intron_variant	Intron 3 of 4
LOC105369736	XR_944866.1	n.305-1527G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.112+124C>T		intron_variant	Intron 3 of 172	5		ENSP00000508949.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59711 AN: 151792 Hom.: 11788 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.373 AC: 116762 AN: 312886 Hom.: 22392 AF XY: 0.374 AC XY: 64155 AN XY: 171490

African (AFR) AF: 0.397 AC: 2989 AN: 7532

American (AMR) AF: 0.337 AC: 5926 AN: 17596

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 2981 AN: 7926

East Asian (EAS) AF: 0.454 AC: 3875 AN: 8538

South Asian (SAS) AF: 0.374 AC: 17752 AN: 47402

European-Finnish (FIN) AF: 0.380 AC: 4036 AN: 10616

Middle Eastern (MID) AF: 0.267 AC: 680 AN: 2546

European-Non Finnish (NFE) AF: 0.373 AC: 73401 AN: 196866

Other (OTH) AF: 0.369 AC: 5122 AN: 13864

GnomAD4 genome AF: 0.393 AC: 59745 AN: 151910 Hom.: 11788 Cov.: 32 AF XY: 0.396 AC XY: 29380 AN XY: 74236

African (AFR) AF: 0.407 AC: 16854 AN: 41450

American (AMR) AF: 0.408 AC: 6228 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2396 AN: 5166

South Asian (SAS) AF: 0.392 AC: 1891 AN: 4820

European-Finnish (FIN) AF: 0.398 AC: 4194 AN: 10540

Middle Eastern (MID) AF: 0.303 AC: 88 AN: 290

European-Non Finnish (NFE) AF: 0.379 AC: 25746 AN: 67906

Other (OTH) AF: 0.386 AC: 811 AN: 2100

Alfa AF: 0.362 Hom.: 5076

Bravo AF: 0.392

Asia WGS AF: 0.406 AC: 1407 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.21
PhyloP100		-1.8
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: rs1820544; hg19: chr12-40793993;