Variant 6-24806467-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001286445.3(RIPOR2):c.3050A>G(p.Asp1017Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,398,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RIPOR2
NM_001286445.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

RIPOR2 (HGNC:13872): (RHO family interacting cell polarization regulator 2) This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

RIPOR2 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
RIPOR2	NM_001286445.3 linkuse as main transcript	c.3050A>G	p.Asp1017Gly	missense_variant	22/22	ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2 linkuse as main transcript	c.3050A>G	p.Asp1017Gly	missense_variant	22/22		NM_001286445.3	A2
RIPOR2	ENST00000259698.9 linkuse as main transcript	c.3113A>G	p.Asp1038Gly	missense_variant	23/23	1		A2	Q9Y4F9-1
RIPOR2	ENST00000613507.4 linkuse as main transcript	c.3113A>G	p.Asp1038Gly	missense_variant	23/23	5		A2	Q9Y4F9-1
RIPOR2	ENST00000538035.6 linkuse as main transcript	c.2963A>G	p.Asp988Gly	missense_variant	22/22	2		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1398144

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689618

show subpopulations

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:

0.00000186

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

The c.3113A>G (p.D1038G) alteration is located in exon 23 (coding exon 22) of the FAM65B gene. This alteration results from a A to G substitution at nucleotide position 3113, causing the aspartic acid (D) at amino acid position 1038 to be replaced by a glycine (G). 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

0.22

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.020

Eigen_PC

Benign

0.0026

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.90

D;.;D;.;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.0

D;.;.;D;.;.

Sift

Uncertain

0.024

D;.;.;D;.;.

Sift4G

Uncertain

0.038

D;.;D;D;.;.

Polyphen

0.67

.;P;P;P;.;.

Vest4

0.39

MutPred

0.25

.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;.;

MVP

0.67

MPC

0.62

ClinPred

0.97

GERP RS

2.0

Varity_R

0.30

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.26

Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over