12-40416791-C-T

Position:

• chr12-40416791-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173600.2(MUC19):​c.1321+432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,786 control chromosomes in the GnomAD database, including 24,255 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 0.56 (24255 hom., cov: 32)
• Consequence: MUC19 NM_173600.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.1321+432C>T		intron_variant
LOC105369736	XR_944868.3	n.167-353G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.1321+432C>T		intron_variant		5		P1
	ENST00000552757.1	n.117+3429G>A		intron_variant, non_coding_transcript_variant		5
MUC19	ENST00000676020.2	n.1374+432C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85507 AN: 151668 Hom.: 24244 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.555

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85566 AN: 151786 Hom.: 24255 Cov.: 32 AF XY: 0.564 AC XY: 41790 AN XY: 74150

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.552

Alfa AF: 0.569 Hom.: 32763

Bravo AF: 0.557

Asia WGS AF: 0.511 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1820545; hg19: chr12-40810593;