NM_020829.4:c.145-9dupA

Variant names:

• chr9-5656572-T-TA
• NM_020829.4:c.145-9dupA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020829.4(RIC1):​c.145-9dupA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000815 in 1,226,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: RIC1 NM_020829.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

Genes affected

RIC1 (HGNC:17686): (RIC1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIC1	NM_020829.4	c.145-9dupA		splice_region_variant, intron_variant	Intron 1 of 25	ENST00000414202.7	NP_065880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIC1	ENST00000414202.7	c.145-11_145-10insA		intron_variant	Intron 1 of 25	5	NM_020829.4	ENSP00000416696.2
RIC1	ENST00000251879.10	c.145-11_145-10insA		intron_variant	Intron 1 of 21	1		ENSP00000251879.6
RIC1	ENST00000418622.7	c.145-11_145-10insA		intron_variant	Intron 1 of 24	5		ENSP00000402240.4
RIC1	ENST00000545641.5	c.-83_-82insA		upstream_gene_variant		1		ENSP00000439488.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.15e-7 AC: 1 AN: 1226252 Hom.: 0 Cov.: 17 AF XY: 0.00000164 AC XY: 1 AN XY: 610964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5656572;