rs889132

Positions:

• chr19-50655132-C-G
• chr19-50655132-C-T

Variant summary

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

The NM_001195076.2(C19orf81):​c.68-918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,994 control chromosomes in the GnomAD database, including 29,778 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 0.61 (29778 hom., cov: 32)
• Consequence: C19orf81 NM_001195076.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

C19orf81 (HGNC:40041): (chromosome 19 open reading frame 81)

SYT3 (HGNC:11511): (synaptotagmin 3) Predicted to enable several functions, including phospholipid binding activity; protein dimerization activity; and syntaxin binding activity. Involved in positive regulation of dendrite extension. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C19orf81	NM_001195076.2	c.68-918C>G		intron_variant		ENST00000425202.6	NP_001182005.1
SYT3	NM_001424346.1	c.-154+2878G>C		intron_variant			NP_001411275.1
C19orf81	XM_047438759.1	c.50-918C>G		intron_variant			XP_047294715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C19orf81	ENST00000425202.6	c.68-918C>G		intron_variant		5	NM_001195076.2	ENSP00000417035.1
C19orf81	ENST00000458538.1	c.-11-918C>G		intron_variant		3		ENSP00000391035.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92974 AN: 151876 Hom.: 29771 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.612 AC: 93007 AN: 151994 Hom.: 29778 Cov.: 32 AF XY: 0.615 AC XY: 45671 AN XY: 74266

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.619

Alfa AF: 0.643 Hom.: 4036

Bravo AF: 0.602

Asia WGS AF: 0.622 AC: 2166 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	8.2
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs889132; hg19: chr19-51158389;