chr12-40483430-T-C

Variant names:

• chr12-40483430-T-C
• rs76180644
• ENST00000454784.10:c.10478T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173600.2(MUC19):​c.10478T>C​(p.Val3493Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 832,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 4/4 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. V3493E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 39)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: MUC19 NM_173600.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.16
• Publications: 0 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]

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 (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173600.2. 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
	MUC19	NM_173600.2		c.10478T>C	p.Val3493Ala	missense	Exon 56 of 172	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	ENST00000454784.10	TSL:5	c.10478T>C	p.Val3493Ala	missense	Exon 56 of 173	ENSP00000508949.1

Frequencies

GnomAD3 genomes Cov.: 39

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 832580 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 384498

African (AFR) AF: 0.00 AC: 0 AN: 15774

American (AMR) AF: 0.00 AC: 0 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3628

South Asian (SAS) AF: 0.00 AC: 0 AN: 16434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00000131 AC: 1 AN: 761426

Other (OTH) AF: 0.00 AC: 0 AN: 27292

GnomAD4 genome Cov.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.086
DANN	Benign	0.25
PhyloP100		-5.2

Splicing

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

Other links and lift over

dbSNP: rs76180644; hg19: chr12-40877232;