14-92513969-C-T

Variant names:

• chr14-92513969-C-T
• NM_024832.5:c.37C>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.37C>T​(p.Pro13Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.428

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=0.07968053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN3	NM_024832.5	c.37C>T	p.Pro13Ser	missense_variant	Exon 1 of 10	ENST00000216487.12	NP_079108.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN3	ENST00000216487.12	c.37C>T	p.Pro13Ser	missense_variant	Exon 1 of 10	1	NM_024832.5	ENSP00000216487.7
RIN3	ENST00000555589.5	n.37C>T		non_coding_transcript_exon_variant	Exon 1 of 9	1		ENSP00000450682.1
RIN3	ENST00000620541.4	c.37C>T	p.Pro13Ser	missense_variant	Exon 1 of 11	5		ENSP00000480603.1
RIN3	ENST00000557762.1	c.37C>T	p.Pro13Ser	missense_variant	Exon 1 of 2	3		ENSP00000452155.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1093414 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 518714

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>T (p.P13S) alteration is located in exon 1 (coding exon 1) of the RIN3 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0032	T;T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N;.;D
REVEL	Benign	0.033
Sift	Benign	0.15	T;.;.
Sift4G	Uncertain	0.029	D;D;.
Polyphen		0.0	B;.;.
Vest4		0.067
MutPred		0.20		Gain of phosphorylation at P13 (P = 0.009);Gain of phosphorylation at P13 (P = 0.009);Gain of phosphorylation at P13 (P = 0.009);
MVP		0.35
MPC		0.27
ClinPred		0.11	T
GERP RS		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.071
gMVP		0.32

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: chr14-92980313;