chr14-92651693-A-T

Position:

• chr14-92651693-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024832.5(RIN3):​c.644A>T​(p.His215Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H215Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117512435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN3	NM_024832.5	c.644A>T	p.His215Leu	missense_variant	6/10	ENST00000216487.12
RIN3	NM_001319987.2	c.419A>T	p.His140Leu	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN3	ENST00000216487.12	c.644A>T	p.His215Leu	missense_variant	6/10	1	NM_024832.5	P2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.41
DANN	Benign	0.87
DEOGEN2	Benign	0.0033	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.039
Sift	Benign	0.046	D;.
Sift4G	Benign	0.38	T;T
Polyphen		0.0010	B;.
Vest4		0.29
MutPred		0.25		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.35
MPC		0.33
ClinPred		0.048	T
GERP RS		-5.5
Varity_R		0.037
gMVP		0.42

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: rs3829947; hg19: chr14-93118038;