rs8109594

Positions:

• chr19-9035796-G-A
• chr19-9035796-G-C

Variant summary

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

The NM_001414686.1(MUC16):​c.355C>T​(p.Pro119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,008 control chromosomes in the GnomAD database, including 6,215 homozygotes. 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.

• Frequency: Genomes: 𝑓 0.27 (6215 hom., cov: 31)
• Consequence: MUC16 NM_001414686.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

Genes affected

MUC16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC16	NM_001414686.1	c.355C>T	p.Pro119Ser	missense_variant	2/94		NP_001401615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40450 AN: 151888 Hom.: 6206 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.266 AC: 40494 AN: 152008 Hom.: 6215 Cov.: 31 AF XY: 0.268 AC XY: 19917 AN XY: 74298

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.244

Alfa AF: 0.201 Hom.: 6622

Bravo AF: 0.262

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8109594; hg19: chr19-9146472;