chr14-92652887-G-C

Variant names:

• chr14-92652887-G-C
• rs12434929
• NM_024832.5:c.1838G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024832.5(RIN3):​c.1838G>C​(p.Gly613Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,034 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (360 hom.)
• Consequence: RIN3 NM_024832.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011604726).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

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.1838G>C	p.Gly613Ala	missense	Exon 6 of 10	NP_079108.3
	RIN3	NM_001319987.2		c.1613G>C	p.Gly538Ala	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.1838G>C	p.Gly613Ala	missense	Exon 6 of 10	ENSP00000216487.7
	RIN3	ENST00000555589.5	TSL:1	n.*1285G>C		non_coding_transcript_exon	Exon 5 of 9	ENSP00000450682.1
	RIN3	ENST00000555589.5	TSL:1	n.*1285G>C		3_prime_UTR	Exon 5 of 9	ENSP00000450682.1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6142 AN: 152174 Hom.: 349 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00632

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0153 AC: 3833 AN: 251148 AF XY: 0.0128

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.00752

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.00814

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.00935 AC: 13669 AN: 1461742 Hom.: 360 Cov.: 36 AF XY: 0.00879 AC XY: 6393 AN XY: 727176

African (AFR) AF: 0.136 AC: 4552 AN: 33480

American (AMR) AF: 0.00823 AC: 368 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00562 AC: 147 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00497 AC: 429 AN: 86258

European-Finnish (FIN) AF: 0.0118 AC: 628 AN: 53278

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5768

European-Non Finnish (NFE) AF: 0.00595 AC: 6620 AN: 1112004

Other (OTH) AF: 0.0142 AC: 859 AN: 60394

GnomAD4 genome AF: 0.0406 AC: 6178 AN: 152292 Hom.: 355 Cov.: 32 AF XY: 0.0398 AC XY: 2963 AN XY: 74470

African (AFR) AF: 0.128 AC: 5316 AN: 41538

American (AMR) AF: 0.0139 AC: 212 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4834

European-Finnish (FIN) AF: 0.0105 AC: 112 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00632 AC: 430 AN: 68024

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0112 Hom.: 22

Bravo AF: 0.0438

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.118 AC: 521

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.0182 AC: 2215

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.00594

EpiControl AF: 0.00670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.00080	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.070	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.49	N
PhyloP100		1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.043
Sift	Benign	0.81	T
Sift4G	Benign	0.92	T
Polyphen		0.012	B
Vest4		0.026
MPC		0.29
ClinPred		0.00052	T
GERP RS		1.3
PromoterAI		0.045	Neutral
Varity_R		0.020
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs12434929; hg19: chr14-93119232;