NM_001286445.3:c.3092A>T

Variant names:

• chr6-24806425-T-A
• NM_001286445.3:c.3092A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286445.3(RIPOR2):​c.3092A>T​(p.Asp1031Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RIPOR2 NM_001286445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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]

ENSG00000282804 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31172687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.3092A>T	p.Asp1031Val	missense_variant	Exon 22 of 22	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3092A>T	p.Asp1031Val	missense_variant	Exon 22 of 22		NM_001286445.3	ENSP00000494268.2
ENSG00000282804	ENST00000562221.1	c.131A>T	p.Asp44Val	missense_variant	Exon 2 of 3	5		ENSP00000455145.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399510 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690258

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	.;T;T;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;.;D;.;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-0.46	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;.;.;N;.;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;.;.;D;.;.
Sift4G	Uncertain	0.0070	D;.;T;T;.;.
Polyphen		0.99	.;D;D;D;.;.
Vest4		0.30, 0.31
MutPred		0.34		.;Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);.;.;
MVP		0.56
MPC		1.1
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.20
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr6-24806653;