chr14-92652478-C-G

Variant names:

• chr14-92652478-C-G
• rs74074812
• NM_024832.5:c.1429C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024832.5(RIN3):​c.1429C>G​(p.Pro477Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 32)
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 6 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1275034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024832.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN3	NM_024832.5	MANE Select	c.1429C>G	p.Pro477Ala	missense	Exon 6 of 10	NP_079108.3
	RIN3	NM_001319987.2		c.1204C>G	p.Pro402Ala	missense	Exon 5 of 9	NP_001306916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN3	ENST00000216487.12	TSL:1 MANE Select	c.1429C>G	p.Pro477Ala	missense	Exon 6 of 10	ENSP00000216487.7
	RIN3	ENST00000555589.5	TSL:1	n.*876C>G		non_coding_transcript_exon	Exon 5 of 9	ENSP00000450682.1
	RIN3	ENST00000555589.5	TSL:1	n.*876C>G		3_prime_UTR	Exon 5 of 9	ENSP00000450682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.056
Sift	Benign	0.11	T
Sift4G	Uncertain	0.010	D
Polyphen		0.91	P
Vest4		0.21
MutPred		0.26		Gain of helix (P = 0.0496)
MVP		0.42
MPC		0.28
ClinPred		0.17	T
GERP RS		3.6
PromoterAI		0.035	Neutral
Varity_R		0.036
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs74074812; hg19: chr14-93118823;