rs754826413

Variant names:

• chr14-92577475-C-A
• NM_024832.5:c.365C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-92577475-C-A
• chr14-92577475-C-T

Variant summary

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

The NM_024832.5(RIN3):​c.365C>A​(p.Ser122*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RIN3 NM_024832.5 stop_gained, splice_region
• Scores: Splicing: ADA: 0.004869
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

RIN3 (HGNC:18751): (Ras and Rab interactor 3) Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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
RIN3	NM_024832.5	c.365C>A	p.Ser122*	stop_gained, splice_region_variant	Exon 3 of 10	ENST00000216487.12	NP_079108.3
RIN3	NM_001319987.2	c.140C>A	p.Ser47*	stop_gained, splice_region_variant	Exon 2 of 9		NP_001306916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.365C>A	p.Ser122*	stop_gained, splice_region_variant	Exon 3 of 10	1	NM_024832.5	ENSP00000216487.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443010 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 718930

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

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

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	35
DANN	Uncertain	0.98
Eigen	Benign	0.038
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.24	N
Vest4		0.13
GERP RS		4.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0049
dbscSNV1_RF	Benign	0.21
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: chr14-93043820;